Evolutionary explanations regarding the differential preference for particular traits hold that preferences arose due to traits’ association with increased potential for reproductive fitness. Assessments of physical attractiveness have been shown to be related to perceived and measured levels of health, an important fitness-related trait. Despite the robust association between physical attractiveness and health observed in the extant literature, a number of theoretical and methodological concerns remain. Specifically, the research in this area possesses a lack of specificity in terms of measures of health, a reliance on artificial social interactions in assessing physical attractiveness, a relatively infrequent use of non-student samples, and has left unaddressed the confounding effects of raters of attractiveness. Using these concerns as a springboard, the current study employed data from the National Longitudinal Study for Adolescent Health (N ≈ 15,000; aged 25 to 34 years) to assess the relationship between physical attractiveness and various specific and overall measures of health. Logistic and OLS regression models illustrated a robust association between physical attractiveness and various measures of health, controlling for a variety of confounding factors. In sum, the more attractive a respondent was rated, the less likely he or she was to report being diagnosed with a wide range of chronic diseases and neuropsychological disorders. Importantly, this finding was observed for both sexes. These analyses provide further support for physical attractiveness as a phenotypic marker of health. The findings are discussed in reference to evolutionary theory and the limitations of the study and future research suggestions are also addressed.
Dr James Higham, senior author, said: "Evolution produces adaptations that help animals thrive in a particular environment, and over time these adaptations lead to the evolution of new species.
"A key question is what mechanisms keep closely related species that overlap geographically from interbreeding, so that they are maintained as separate species.
"Our findings offer evidence for the use of visual signals to help ensure species recognition: species may evolve to look distinct specifically from the other species they are at risk of interbreeding with," Dr Higham said.
"In other words, how you end up looking is a function of how those around you look. With the primates we studied, this has a purpose: to strengthen reproductive isolation between populations."
1Stony Brook University, Stony Brook, New York, USA, 2University of Michigan, Ann Arbor, Michigan, USA
1Harvard Medical School, Boston, USA, 2Broad Institute, Cambridge, USA, 3Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
As a first step, we have developed a statistical method for inferring segments of Neandertal local ancestry in modern humans and applied this method to construct a map of Neandertal ancestry in modern non-Africans, using data from Phase 1 of the 1000 genomes project combined with a high coverage (50×) Neandertal genome. This map reveals the adaptive impact of Neandertal gene flow as we find enhanced Neandertal ancestry in genes involved in keratin filament formation as well as other biological pathways. We also observe large regions with reduced Neandertal ancestry consistent with purifying selection against introgressing Neandertal alleles in part due to these alleles contributing to hybrid male sterility.
To extend this approach to other archaic-modern human introgression events, we generated deep genome sequences of 21 people from populations with substantial Denisovan ancestry: 16 Papua New Guineans, 2 Bougainville Islanders, and 3 aboriginal individuals from Australia. We also extend our method to infer Neandertal and Denisovan local ancestry in these populations. We test whether the same evidence for hybrid male sterility is observed in this introgression event as is observed between Neandertals and modern humans.
1CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China, 2Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany
In the last few years a number of genome-wide scans for signals of recent natural selection have been done for the human genome. These studies strongly furthered our understanding of recent human evolution. Nonetheless, some key issues were left largely un-solved. In this study, several coalescent based likelihood tests were developed to collectively assign all genome fragments to modes of neutrality, negative, balancing or positive selection, and simultaneously estimate the selection time and coefficient. Simulations revealed that this workflow was powerful towards various non-neutral evolutions, while remaining highly robust against demographic factors. Here we report a fine atlas of natural selection in the human genome through analyze the 1000 Genomes data. Several hundreds of regions undergone positive selection and a bunch of regions undergone negative and balancing selection were detected. We did functional annotation for genes undergone selection in various categories. Genes were enriched in certain functional groups. And we found that there is high heterogeneity of selection time of positive selection genes in different functional categories. We also evaluated the selection pressures in ENCODE predicted regulatory elements. The selection pressure in promoter regions was the highest, whereas introns and repressed or low-activity regions showed obviously lower influence of selection. Spatial distribution revealed that TSS and CDS clearly centered in the selection signals. Given the fine resolution of the selection signals, we are in the process of understanding the different selection pressures our ancestors have encountered during the course of recent migration, local adaptation and social transitions.
Museum National d'Histoire Naturell, Paris, France
1Department of Genetics, Rutgers University, Piscataway, NJ, USA, 2Department of Biology, Bloomington, IN, USA
1University of Puerto Rico at Mayaguez, Puerto Rico, Puerto Rico, 2IBIOS Graduate Program Option In BioInformatics and Genomics, The Huck Institute of Life Sicences, Pennsylvania State University, University Park, Pennsylvania, USA, 3Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA, 4Department of Biology, University of Puerto Rico at Rio Piedras, San Juan, Puerto Rico, Puerto Rico, 5Caribbean Genome Center, Biology Department, University of Puerto Rico at Mayaguez, Mayaguez, Puerto Rico, Puerto Rico
1University of Pennsylvania, Philadelphia, PA, USA, 2UMR 208, IRD-MNHN, Musée de l’Homme, 75116 Paris, France, 3Dipartimento di Biologia Ambientale, Universita’ La Sapienza, Roma, Italy, 4Division of Anatomical Pathology, Department of Pathology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, 7505, South Africa, 5Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, 15-13 Khartoum, Sudan, 6Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, 7Kenya Medical Research Institute, Centre for Biotechnology Research and Development, 54840-00200 Nairobi, Kenya, 8Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
1Genetics Department, Stanford University, Stanford, CA, USA, 2Department of Biological Sciences, Stanford University, Stanford, CA, USA, 3Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa, 4Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, 5Department of Ecology and Evolution, SUNY Stony Brook, Stony Brook, NY, USA
CEFE - CNRS, Montpellier, France
1CNRS/MNHN/P7 UMR7206, Paris, France, 2INRA/CNRS UMR 0320/UMR 8120, Moulon, France, 3CNRS/Univ Toulouse UMR5288, Toulouse, France, 4Academy of Science, Tachkent, Uzbekistan, 5Academy of Science, Bishkek, Kyrgyzstan
We hypothesized that the mechanism by which such reduction in effective population size can be reached is Cultural transmission of reproductive success. Building on our previous theoretical work that showed that CTRS can reduce profoundly effective population size, and on a method that we have designed to detect such transmission from current DNA sequence polymorphism datasets, we tested formally the extent to which CTRS reduces genetic diversity in Central Asia, where we have previously demonstrated the occurrence of sex-specific reduction in effective population size: male effective size is much smaller than its female counterpart.
We used mtDNA and Y-chromosome genetic data to infer male and female transmission of reproductive success in 19 Turkic and Indo-Iranian populations from Central Asia known for their contrasted social organisations. Both societies are patrilocal and mildly polygynous, but Turkic populations have a patrilineal descent, while Indo-Iranian populations have a cognatic descent.
Our results show that patrilinearity impacts genetic diversity through cultural transmission of reproductive success. This clearly demonstrates the impact of social organization on human biological evolution. Moreover, notwithstanding the fact that our genetic approach clearly shows that there is a strong male bias transmission of reproductive success in patrilineal societies, it also formally demonstrates that cultural transmission of reproductive success could be a major evolutionary force. Indeed, it reduces within-population genetic diversity and increases among-population differentiation, the two key components for the evolution of cooperation.
Stanford University, California, USA
We investigate the roles of vertical, oblique, and horizontal learning of a fitness-altering cultural trait and ﬁnd that, compared to vertical learning alone, horizontal and oblique learning can accelerate the trait’s spread, lead to faster population growth, and increase its equilibrium frequency.
1Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 2Harvard Medical School, Boston, USA, 3Broad Institute, Boston, USA
Uppsala University, Uppsala, Sweden
University of Florida, Gainesville, FL, USA
The Health Equity Alliance of Tallahassee (HEAT) Heart Health Study is a community-based participatory research (CBPR) design that engages community members in the planning and collection of research data. A primary aim of HEAT is to investigate the socio-cultural factors that contribute to disparity in health status, especially in regard to cardiovascular phenotypes. Extensive cultural survey data targeted at understanding neighborhood environment, socioeconomic status, exposure to discrimination, and other stressors as well as phenotypic measures of body composition and blood pressure were completed on 165 African American research participants from economically diverse neighborhoods in Tallahassee, Florida. DNA derived from saliva samples was collected and genotyped on a custom Affymetrix Axiom array to assay a large panel of ancestry informative markers for assessment of genomic admixture and to perform genomic admixture mapping (3,600 AIMs). Additionally, this array includes SNPs in previously reported candidate genes for blood pressure, stress, and skin pigmentation (over 25,000 candidate SNPs). This work aims to address the complex interplay of genetic influences, including candidate genes and genetic ancestry, and socio-cultural factors, such as stress caused by perceived discrimination and community support, on blood pressure variation. We have previously shown that genetic contributions to variation in blood pressure phenotypes are modified by the inclusion of socio-cultural data. The more detailed study design made possible by this interdisciplinary CBPR study reveals the complex interplay of the genome and culture in contributing to health disparities in complex phenotypes.
1CNRS/MNHN/Univ. Paris Diderot/Sorbonne Paris Cite, Paris, France, 2Stanford University, Department of Biology, Stanford, CA, USA, 3University of Manitoba,Department of Biochemistry and Medical Genetics, Winnipeg, MB, Canada, 4University of Michigan, Departments of Linguistics & Afroamerican and African Studies, Ann Arbor, MI, USA
1Baylor College of Medicine, Houston, TX, USA, 2Texas Children's Hosptial, Houston, TX, USA
1NIH/NIAAA, Section of Comparative Behavioral Genomics, Rockville, MD, USA, 2NIH/NICHD, Section of Comparative Ethology, Poolesville, MD, USA
1University of California - Berkeley, Berkeley, CA, USA, 2Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
Though the recent sequencing of the high-coverage Denisovan and Neanderthal genomes has allowed us to find the genetic differences that set modern humans apart from archaic humans, the subset of such changes that rose to fixation due to selection is currently unknown. In this study, we look for patterns of positive selection on the modern human lineage at various classes of putatively functional changes using diversity scaled by divergence, as has been done previously on the human lineage since the split from chimpanzees. We also develop an approximate Bayesian computation (ABC) approach incorporating various statistics aimed at identifying ancient patterns consistent with selection around a candidate site. We fail to find an enrichment for signals of positive selection around nonsynymous changes relative to synonymous changes. It has been argued that the failure to detect this difference in changes on the human lineage may be due to varying levels of background selection which occlude the signal of positive selection. Indeed, when we control for the intensity of background selection (BS), we observe a significant difference between nonsynonymous changes in regions of low BS and matching regions of the genome, lending support to this hypothesis. We also identify a slight enrichment for positive selection at splice site changes.
University of Pennsylvania, Philadelphia, PA, USA
1CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences,Chinese Academy of Science, Shanghai, China, 2Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
1Stellenbosch University, Department of Molecular Biology and Human Genetics, Tygerberg, Cape Town, South Africa, 2Stony Brook University, Department of Ecology and Evolution, Stony Brook, New York, USA, 3Stanford University, Department of Biology, Stanford, California, USA, 4University of California,, Los Angeles, California, USA, 5Stanford University, Department of Genetics, Stanford, California, USA
The Cape Coloured population of Cape Town, South Africa (SAC) derives ancestry from multiple, global populations including Europeans and Indonesians. Initial studies also indicated a substantial contribution from the KhoeSan, a diverse group of hunter-gatherers and pastoralists that historically occupied much of southern Africa (Chimusa et al. 2013a, de Wit et al. 2010). The degree of KhoeSan ancestry reflects the role of indigenous KhoeSan in the early establishment of the SAC population (Mountain 2003). Furthermore, we have demonstrated significant evidence of an association between KhoeSan ancestry and Tuberculosis (TB) susceptibility that is not confounded by socio-economic status. It was additionally found that the KhoeSan ancestry component in the SAC seems to contribute to the extreme susceptibility to TB in this admixed population. The southern African KhoeSan fall into two genetic groups, roughly corresponding to the northwestern and southeastern Kalahari, which has been shown to have separated within the last 30,000 years (Pickrell et al. 2013). We collected DNA samples from the Nama along the western coast and the Khomani San from the Kalahari Desert (written informed consent and approval of the Human Research Ethics Committee of Stellenbosch University). SNP genotype data was generated on the Illumina OmniExpress platforms (700k- 1M array) for 120 Khomani San, 25 Cape Coloureds and 13 Nama. Whole genome sequencing data of an additional 106 Nama samples is currently underway by collaboration with the Welcome Trust Sanger Institute. This is to our knowledge the largest genome-wide dataset collected for the purpose of understanding South African genetic diversity. We use principal component analysis, chromopainter and ADMIXTURE to investigate fine sale population structure among these South African groups.
Cornell University, Ithaca, NY, USA
1Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia, 2Ugra State University, Khanty-Mansiisk 628012, Russia, 3Ugra Research Institute of cellular technology with stem cell bank, Khanty-Mansiisk 628011, Russia
To explore genetic structure of the region described we analyzed single nucleotide polymorphism in the populations mentioned above using different versions of Illumina BeadChips. Principal components analysis, ADMIXTURE clustering and Wright's fixation indices (FST) were used to probe genetic variation.
Mansi were indigenous inhabitants of Northern European area till 17th Century AD. This ethnic group has undergone trans-Uralic migration and nowadays inhabits Sub-Arctic Region of Western Siberia. The Khanty, closely related to Mansi by linguistic classification, are the indigenous inhabitants of this region. The Mansi and the Khanty peoples have genomic characteristics that the most distant from all others by presence of different ancestry component.
Komi live in the farthest corner of Northern-Eastern Europe. Based on genomic analysis Komi form separate pole of genetic diversity in northern Europe gene pool. Modern Finno-Ugric minority, the Veps, which is one of the oldest people of northern Europe, still inhabit some territories of northwest Russia, demonstrates genetic similarity both with Finns and Komi.
Russians are the most abundant people in Northern-Eastern Europe. Principal component analysis has shown significant differences between Russians of Northern European region and Russian populations from the central part of Russian Plain. The later Russian populations have formed a single cluster on PC plot. In contrast, Northern Russians have demonstrated close relationships with Veps' population.
In general, our data provide a more complete genetic map of Europe and adjacent Northern area accounting for the diversity in its most eastern and northeastern populations. Furthermore, these data contribute to a better understanding of the population genetic history of present day ethnic groups of the area studied.
1Stanford University, Stanford, CA, USA, 2Brown University, Providence, RI, USA
In addition to being of fundamental interest, the presence of sex-bias affects demographic inference. Sex-bias, either in the male or female direction, decreases the effective population size of the X chromosome as well as the autosomes of a population. If this reduction in effective population size is unaccounted for, demographic parameters estimates (e.g., bottleneck times or divergence times) will be inflated. We assess the effect of cryptic sex-bias on the estimation of demographic parameters using simulated data. We propose a correction based on the joint inference of demographic parameters from the X chromosome and the autosomes. These analyses give us a more complete picture of the presence and effect of human sex-biased demography and can be easily applied to other organisms.
1University of Arizona, Tucson, AZ, USA, 2University of California, San Francisco, CA, USA, 3University of Pennsylvania, Philadelphia, PA, USA
To identify candidate introgressive loci, we scan the genomes of 16 individuals and calculate S*, a summary statistic that was specifically designed by one of us (JDW) to detect archaic admixture. The significance of each candidate is assessed through extensive whole-genome level simulations using demographic parameters estimated by ∂a∂i to obtain a parametric distribution of S* values under the null hypothesis of no archaic introgression. As a complementary approach, top candidates are also examined by an approximate-likelihood computation method. The admixture time for each individual introgressive variant is inferred by estimating the decay of the genetic length of the diverged haplotype as a function of its underlying recombination rate. A neutrality test that controls for demography is performed for each candidate to test the hypothesis that introgressive variants rose to high frequency due to positive directional selection. The present study represents one of the most comprehensive genomic surveys to date for evidence of archaic introgression to anatomically modern humans in Africa.
1Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark, 2Faculty of Archaeology, Leiden University, Leiden, The Netherlands, 3Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden, 4Center for Computational, Evolutionary and Human Genomics, Stanford, California, USA, 5Instituto de Ciencias Forenses 'Luís Concheiro', Universidade de Santiago de Compostela, Santiago de Compostela, Spain
1Harvard Medical School, Boston MA, USA, 2Broad Institute of Harvard and MIT, Boston MA, USA, 3Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 4Stony Brook University, Stony Brook NY, USA, 5University of Helsinki, Helsinki, Finland, 6University of Chicago, Chicago IL, USA, 7Departament de Ciències Experimentals i de la Salut, Barcelona, Spain, 8University of Arizona, Tuscon AZ, USA, 9University College, London, UK, 10University of California San Francisco, San Francisco CA, USA, 11University of Cambridge, Cambridge, UK, 12University of Pennsylvania, Philadelphia PA, USA, 13University of Utah, Salt Lake City Utah, USA, 14Russian Academy of Science Siberian Branch, Novosibirsk, Russia, 15Estonian Biocentre, Tartu, Estonia, 16Simons Foundation, New York, USA
We have generated whole genome sequences (>30x average) in 280 individuals from 135 worldwide populations, using an identical protocol at a single facility (Illumina, Ltd.). In addition we have built an informatics pipeline geared towards population genetics that eliminates biases in standard pipelines that might confound population genetics analyses.
We compute a maximum likelihood estimate for the population mutation rate (heterozygosity) in each population using mlrho (Haubold et al. Mol. Ecol. 2010). This provides precise information about how heterozygosity varies across diverse worldwide human populations. These data can be used to test more powerfully the extent to which a serial founder model is sufficient to explain the empirically observed decline in heterozygosity with distance from Africa.
1Department of Genetics, Harvard Medical School, Boston, MA, USA, 2Broad Institute, Cambrige, MA, USA, 3Institute for Archaeological Sciences, University of Tübingen, Tübingen, Germany, 4Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 5Department of Genome Sciences, University of Washington, Seattle, WA, USA, 6Department of Integrative Biology, University of California, Berkeley, CA, USA, 7Johannes Gutenberg University Mainz, Institute of Anthropology, Mainz, Germany, 8Archaeological Research Laboratory, Stockholm University, Stockholm, Sweden, 9Estonian Biocentre, Evolutionary Biology group, Tartu, Estonia
Our main findings are: (i) early European farmers were of mainly Near Eastern ancestry but with substantial European hunter-gatherer ancestry; (ii) European hunter-gatherers fall outside extant European variation in the direction of Near Eastern-European differentiation, (iii) most modern Europeans do not appear to be a simple mixture of the early European farmers and hunter-gatherers, but rather to have ancestry from at least three ancestral populations: (i) EEF: early European farmers (like the Stuttgart individual), (ii) WHG: west European hunter-gatherers (like the Loschbour and La Brana individuals), and (iii) ANE: ancient North Eurasians (like the Mal'ta individual). Mediterranean populations like Sardinians most closely resemble EEF individuals, while Baltic populations like Lithuanians most closely resemble WHG individuals.
Unexpectedly, all present-day eastern non-African groups (Oceanians, East Asians, Onge from the Indian Ocean, and Native Americans) are genetically closer to Eurasian hunter-gatherer groups than to the Stuttgart individual. We propose a model of Eurasian prehistory in which EEF possessed a fraction of ancestry from a basal Eurasian population that split off from other Eurasians prior to the split between Eurasian hunter-gatherers and eastern non-Africans.
The Scandinavian Motala hunter-gatherers are the only ancient population showing evidence of ANE ancestry, yet such ancestry is pervasive in present-day populations from both Europe and the Near East. This suggests that ANE ancestry spread across much of West Eurasia after the early Neolithic. Additional migrations from the Near East and East Eurasia affected more limited subsets of Europeans from the Mediterranean and Northeastern Europe respectively.
Our results suggest a dynamic history of the emergence of modern Europeans in which the Neolithic-Mesolithic admixture played a major role, but was supplemented by later admixture processes.
1Department of Genetics, Harvard Medical School, Boston, MA, USA, 2Broad Institute of Harvard and MIT, Cambridge, MA, USA, 3Peabody Museum of Archaeology and Ethnology, Harvard University, Cambridge, MA, USA
1Division of Biological Anthropology, University of Cambridge, Cambridge, UK, 2Centre for GeoGenetics, University of Copenhagen, Copenhagen, Denmark, 3Faculty of Archaeology, Leiden University, Leiden, The Netherlands, 4Institute of Evolutionary Biology, Pompeu Fabra University, Barcelona, Spain, 5Institute of Patagonia, University of Magallanes, Punta Arenas, Chile, 6Autonomous University of Barcelona, Barcelona, Spain, 7Department of Biology, University of Florence, Florence, Italy, 8ITB CNR Institute for Biomedical Technologies, National Research Council, Milan, Italy, 9Department of Environmental Biology, University of Rome La Sapienza, Rome, Italy, 10Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy, 11Department of Archaeology, University of Winchester, Winchester, UK
The Fuegians lived on the islands of Tierra del Fuego in the Southern Cone of South America in isolation from other Native Americans until their extinction at the beginning of the 20th century, likely maintaining their original genetic signature without recent admixture. Based on the Fuegian robust cranial morphology, a few controversial studies have suggested that Fuegians might be descendants of a putative earlier migration wave preceding the arrival of the other Native Americans.
Using target enrichment and next-generation sequencing, we obtained complete mitochondrial genomes from skeletal remains of 37 Fuegians and 19 individuals from adjacent Patagonia. Comparing them to published sequences of other Native Americans, we estimated the divergence times and past population dynamics in the Southern Cone and we assessed the question of population continuity in the region. The coalescent ages of deep Fuegian-specific clades suggest early human settlement in Tierra del Fuego, probably associated with the initial peopling of the continent. The early arrival of Fuegians to the Southern Cone is consistent with the generally accepted scenario of rapid coastal dispersal throughout the Americas, which is further supported by the presence of Monte Verde, the oldest known South American pre-Clovis archaeological site, in Chilean Patagonia. In this presentation, alternative views on Fuegian origins and their genetic affinities with other Native Americans are considered in the context of the evolutionary history of South American populations.
1Harvard Medical School, Boston, MA, USA, 2Brigham and Women's Hospital, Boston, MA, USA
1Harvard Medical School, Boston, USA, 2Broad Institute of MIT and Harvard, Cambridge, USA, 3Harvard University, Cambridge, USA
1Howard Hughes Medical Institute, Boston, MA, USA, 2Harvard Medical School, Boston, MA, USA, 3Broad Institute of Harvard and MIT, Cambridge, MA, USA
1Centre for GeoGenetics, Natural History Museum of Denmark, Copenhagen, Denmark, 2Uppsala University, Uppsala, Sweden, 3University of California - Berkeley, Berkeley, California, USA, 4University of Copenhagen, Copenhagen, Denmark, 5University of Chicago, Chicago, Illinois, USA, 6Pennsylvania State University, University Park, Pennsylvania, USA
New World Arctic (North America and Greenland) was first occupied by modern humans around 5,000 years ago. The PaleoEskimos constituted the first two cultures to have peopled the region: the Pre-Dorset or Saqqaq culture (ca. 3000-800 BC) and the Dorset culture (ca. 800 BC-1300 AD). The NeoEskimos (Thule culture), who are considered to be ancestral to modern-day Inuit, were the latest migrants into the New World Arctic and spread eastwards from northern Alaska in around 1000 AD. However, despite decades of archaeological research having established when the cultural transitions occurred, there is no consensus on how these people were related to one another and whether one or several gene pools were represented in these different Arctic traditions. We present results from an ongoing study comprising the largest genomic dataset generated thus far on ancient human samples from sites in Siberia, Alaska, Canada and Greenland. Our research contributes new perspectives to the debate of cultural versus genetic replacement in the New World Arctic and also evaluates the extent to which the PaleoEskimos and the NeoEskimos have shaped the genetic structure of modern populations in the region.
Indiana University, Bloomington, IN, USA
McGill University, Montreal, Qc, Canada
1Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden, 2Master Biosciences, École Normale Supérieure de Lyon, Lyon, France, 3Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of 11 the Witwatersrand, and National Health Laboratory Service, Johannesburg, South Africa, 4Science for Life Laboratory, Uppsala University, Uppsala, Sweden
We sequenced the LCT regulatory region in 267 individuals from 13 populations: 7 Khoe and San groups, the ancestral inhabitants of southern Africa, 3 Bantu-speaking groups and 3 groups with mixed ancestry. Those groups have diverse subsistence patterns. We then searched for signals of past East-South African admixture events using DNA chip data including many Eastern and Southern African populations as well as HapMap reference populations.
We found two previously described lactase persistence alleles in our sample: the European 13910C>T allele in individuals with recent European admixture and the East African 14010G>C allele in the Nama (at a frequency of 35.7% if recently admixed individuals are removed) and in other groups with lower frequency. The Nama are a Khoe group and are pastoralist. To learn about the origin of this variant in southern Africans, we analysed a 54.6 kb window of DNA chip data including the two SNPs. It showed that the 14010C allele in the Nama is on the same haplotype as in the East African Maasai; hence, we concluded that the allele appeared only once, likely in the Eastern Africans (greater frequencies) and then it was brought to southern Africa. Thanks to an ADMIXTURE analysis we identified an East African component in several Khoe-San groups; again, the highest percentage of East African ancestry (~13%) is found in the Nama. This admixture event likely took place after the 14010C allele appeared in East Africans, ie ~3,000–7,000 years BP.
In a nutshell, we investigated a South-East African migration event combining information on a single trait and genome-wide data. This event explains the presence of an East African allele in Khoe-San groups. The groups with the largest East African component are the pastoralist groups, in which being able to digest milk is advantageous. Our findings provide new elements about ancestral migrations and spreading of pastoralism in Africa and complement conclusions of other fields, like archaeology.
23andMe, Inc., Mountain View, CA, USA
1The Hebrew University of Jerusalem, Jerusalem, Israel, 2Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 3University of Oviedo and CNB-CSIC, Oviedo, Spain, 4University of Cantabria, Santander, Spain
Additionally, we found several genes that are imprinted in present-day humans but are methylated in archaic humans. This includes H19, a gene that encodes a long non-coding RNA that is maternally imprinted in present-day humans. When imprinting is damaged, methylation of this gene causes the Beckwith-Wiedrmann syndrome, whose symptoms include growth dysregulation, increased susceptibility to cancer and facial features such as a prominent lower jaw and midfacial hypoplasia. Unlike present-day humans and the Denisovan, in the Neandertal the promoter of H19, as well as the imprinting-control region (ICR), are both completely methylated. Methylation of the H19 promoter was previously shown to anti-correlate with its expression levels, suggesting that H19 might have had reduced activity in the Neandertal. Interestingly, H19 was also found to be differentially methylated in Orangutans. This gene is one of several examples where altered methylation in present-day humans results in abnormal symptoms, whereas in the Neandertal, to our knowledge, the symptoms do not come to realization.
Another differentially methylated gene between archaic and modern humans is AUH. Defects in AUH are behind the methylglutaconic aciduria type I syndrome, whose symptoms include speech delay, poor articulation, and forgetfulness. This gene is unmethylated in present-day humans, but is methylated in archaic humans, suggesting differential regulation in both archaic humans. As this gene shows constant methylation levels across 25 human tissues, it is possible that these differences in methylation extend to the brain tissue as well.
Such trends in methylation shed light on the evolutionary constraints that are behind epigenetic regulation in the human lineage and on the mechanisms that lead to disease symptoms in one human group and to a completely healthy individual in another.
1Pennsylvania State University, University Park, PA, USA, 2University of California, Los Angeles, Los Angeles, CA, USA, 3University of California, Berkeley, Berkeley, CA, USA
1Arizona State University, Tempe, AZ, USA, 2University of Miami, Coral Gables, FL, USA
We present the results of pilot research focused on retrieving ancient DNA from human skeletal remains from Puerto Rico. We performed DNA extraction on 43 individuals from three pre-Columbian Puerto Rican sites dated between 590 to 1280 cal AD. We tested our extracts for the presence of ancient DNA through PCR amplification of an 80 bp fragment of mitochondrial DNA (mtDNA). This preliminary assessment indicates that 42% (n=18) of our samples have amplifiable mtDNA.
However, extensive DNA fragmentation and degradation may affect amplification efficiency in these samples. With the aim of overcoming these issues, we converted 18 of our extracts into sequencing libraries, and enriched them by targeting complete mitochondrial genomes. Preliminary quality assessments with fragment analysis and quantitative PCR methods suggest that we have successfully captured ancient mtDNA in no less than nine of our sequencing libraries.
The recovery of complete mtDNA genomes from these individuals will allow us to begin to characterize the genetic diversity and population history of a pre-Columbian Antillean population. These data may also be used to help estimate the contribution that these ancient groups played in shaping the genetic ancestry of modern Puerto Ricans.
1University of Chicago, Chicago, USA, 2Institute of Evolutionary Biology (UPF-CSIC), PRBB, Barcelona, Spain, 3Howard Hughes Medical Institute, Stanford University, Stanford, USA, 4Departments of Biology and Genetics, Stanford University, Stanford, USA
1University of Chicago, Chicago, IL, USA, 2Penn State University, University Park, PA, USA, 3Case Western Reserve University, Cleveland, OH, USA, 4University of Michigan, Ann Arbor, MI, USA, 5Addis Ababa University, Addis Ababa, Ethiopia, 6SUNY Stony Brook, Stony Brook, NY, USA, 7Stanford University, Stanford, CA, USA
In this study, we focus on African demography, specifically the population structure in Africa going back in time and the dynamics of the Out-of-Africa event. To address these questions, we assembled a dataset with whole genome sequences from 162 individuals using some in-house sequencing and publicly available sources such as the 1000 Genomes project. These samples span twenty two populations worldwide. These include eleven African populations which we use to examine the population substructure in Africa. In addition, we also have 2 Middle Eastern, 5 European and 4 East/Central Asian populations which allows us to estimate the timing of the Out-of-Africa event and the European-Asian split.
We find extensive population structure in Africa extending back to before the Out-of-Africa event. The Ethiopian populations show gene flow back from 15kya, with the Maasai and Luhye merging with the east African populations ~40kya. We find evidence for extensive mixing between east and west African populations beginning 50kya. Among the pygmy populations, we see recent gene flow between the Batwa and Mbuti. All the African populations except for the San merge into a single population around 100 kya. The San exchange migrants with the other African populations starting ~120 kya. We estimate the Out-of-Africa event to have occurred ~75kya and the European-Asian split to ~25kya. Our findings also suggest a period of sustained gene flow between East Africa and Middle Eastern populations after the Out-of-African event.
Stanford University, Stanford, CA, USA
We propose random projections as a fast and scalable way of performing dimensionality reduction of large genome-wide SNP datasets. With a sparse implementation, we show that projections can be computed in time linear in the size of the dataset. Using 20,000 individuals simulated from the HapMap Phase 3 CEU, ASW, CHB and YRI populations at 365,466 SNPs, we show that the projected individuals can be used to (a) perform PCA (b) accelerate convergence of model-based ancestry inference (b) compute identity-by-state distance. These projections have the following properties: (a) by definition, the projection directions are independent of the data and hence are robust to outliers (b) existing projections do not need to be recomputed if individuals are added to or removed from the dataset (b) the theoretical upper bound on the number of projections required to summarize a dataset is nearly independent of the number of SNPs in the dataset and is proportional to the logarithm of the number of individuals in dataset. In addition, for large GWAS, where sequencing/genotyping data may be distributed across multiple physical locations, random projections can be computed and shared instead of sharing the genotype data directly. This can reduce data sharing requirements by one/two orders of magnitude.
1Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark, 2Department of Archaeology, La Trobe University, Melbourne, Australia, 3Center for Computational, Evolutionary and Human Genomics, Stanford University, Stanford, USA, 4Centro de Investigación Sobre la Evolución y Comportamiento Humanos, Universidad Complutense de Madrid, Madrid, Spain, 55Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden, 6Instituto Nacional de Antropología e Historia, Mexico City, Mexico, 7Anthropological Institute, University of Zurich, Zurich, Switzerland, 8Laboratoire Eco-Anthropologie et Ethnobiologie, Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Université Paris 7, Heyer, France
Although multiple lines of evidence support the notion that the origin all extant Amerindian populations is of Asian origin, the number of migrations and source populations that gave rise to the first inhabitants of the New World is still contentious. Based on the significant craniofacial discontinuity between the Pleistocene (Paleoamerican) and Holocene (Amerindian) populations, it has been suggested that the Americas were populated twice, from different Asian sources. Under this assumption, a first migration wave originating from Southeast Asia gave rise to the Paleoamericans, whereas all modern Amerindian groups would derive from a second wave of migration originating in Northeast Asia. Pericues in Baja California, Mexico, and the very southern populations of Patagonia and Tierra del Fuego display Paleoamerican craniofacial traits leading some researchers to suggest that these are a temporal extension of the first colonizers of the Americas. We have shotgun sequenced DNA from skeletal remains of Pericues and Fuegans to assert their genetic affinity to modern populations.
Stanford University, Stanford, CA, USA
1Evolutionary biology group, Estonian Biocentre, Tartu, Estonia, 2Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia, 3Estonian Genome Center, University of Tartu, Tartu, Estonia, 4Department of Bioinformatics, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia, 5Department of Biological Anthropology, University of Cambridge, Cambridge, UK, 6Department of Integrative Biology, University of California Berkeley, Berkeley, USA, 7Human Genetics Group, Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenia, 8Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and Herzegovina, 9Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Russia, 10Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia, 11Institute of Internal Medicine, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia, 12Laboratory of Molecular Biology, North-Eastern Federal University, Yakutsk, Russia, 13Institute of Genetics and Cytology, National Academy of Sciences, Minsk, Belarus, 14Laboratoire d'Anthropologie Moléculaire et Imagerie de Synthèse, Centre National de la Recherche Scientifique, Université de Toulouse, Toulouse, France, 15Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia, 16Research Department of Genetics, Evolution and Environment, University College London, London, UK, 17Center for GeoGenetics, University of Copenhagen, Copenhagen, Denmark
We present here initial results from population genetic analyses on the data.
We use recently developed methods based on length distributions of shared genomic segments to estimate the dynamics of past effective population sizes of regional populations, population split times and subsequent admixture events between various Eurasian population pairs.
We map the geographic and temporal variation of Neanderthal and Denisova introgression among different Eurasian populations.
For Y chromosome data we determined the regions of highest mapping quality and applied phylogenetic methods to determine the order and temporal dynamics of branching events in non-African Y chromosome haplogroups. We show that the relatively short branch lengths distinguishing continental non-African populations are consistent with the model of a rapid initial colonization of Eurasia and Oceania.
University of Pennsylvania, Philadelphia, PA, USA
Departments of Genetics and Biology, University of Pennsylvania, Philadelphia, PA, USA
Africa is thought to be the ancestral homeland of all modern human populations. It is also a region of tremendous cultural, linguistic, climatic, and genetic diversity. Despite the important role that African populations have played in human history, they remain one of the most underrepresented groups in human genomics studies. A comprehensive knowledge of patterns of variation in African genomes is critical for a deeper understanding of human genomic diversity, the identification of functionally important genetic variation, the genetic basis of adaptation to diverse environments and diets, and the origins of modern humans. Furthermore, a deeper understanding of African genomic variation will provide the necessary foundation for powerful and efficient genome-wide association and systems biology studies to identify coding and regulatory variants that play a role in phenotypic variation including disease susceptibility. We have used whole genome SNP genotyping and high coverage sequencing analyses to characterize patterns of genomic variation, ancestry, and local adaptation across ethnically and geographically diverse African populations. We have identified candidate loci that play a role in adaptation to infectious disease, diet and high altitude, as well as the short stature trait in African Pygmies. Additionally, our studies shed light on human evolutionary history and African population history.
1University of Pennsylvania, Philadelphia, PA, USA, 2Cornell University, Ithaca, NY, USA, 3Vanderbilt University, Nashville, TN, USA, 4Addis Ababa University, Addis Ababa, Ethiopia, 5Musee de L’Homme, Paris, France, 6Integral Molecular, Philadelphia, PA, USA, 7Kenya Medical Research Institute, Nairobi, Kenya, 8Ministry of Scientific Research and Innovation, Yaounde, Cameroon, 9Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, 10National Institute on Deafness and Other Communication Disorders, NIH, Rockville, MD, USA, 11Monell Chemical Senses Center, Philadelphia, PA, USA, 12Rutgers University, New Brunswick, NJ, USA
Inter American University of Puerto Rico, Bayamon, Puerto Rico
Post-sampling the assessment of skeletal sample condition was used to select material chosen for genetic analysis, and 44% of the skeletal population was selected for analysis. The morphology of samples was assessed and 87% of bones and teeth were considered to be in good or fair condition. A novel technique, Qualitative Light Fluorescence, was also used to compare the teeth to modern standards, showing a loss of 21.8% in fluorescence and indicating inorganic degradation. Histological sections taken from non-human bone finds from the site generally varied less than that indicated by the gross morphology, showing good to excellent preservation.
Well preserved skeletal samples were selected for detailed investigations into the biological and chemical condition, principally through amino acid racemisation, amino acid composition, heavy metal analysis. All samples tested had D/L Aspartic acid ratio less than 0.1, although 50% of the samples had a ratio over 0.08, which indicated that the recovery of DNA from these skeletal samples was feasible, although degraded. The element profiles showed no discernable anomalies, either due to diet or diagenesis. To consolidate genographic research, strontium isotope analysis of a small population subset, showed three anomalous ratios, which indicated widespread contact in North Atlantic Europe and unexpected residence patterns
DNA recovery was more successful in teeth than in bones. Amplification over several rounds using various primers specific for human HV1 & 2 mtDNA was conducted. Of all the samples only 14.8% of the skeletal teeth samples were amplified, although over 90% of the screened sampled were amplified and sequenced. DNA spiking trials demonstrated that some of the samples were affected by inhibition and poor template condition as validated by sequencing. Independent confirmation of successful samples was attained by sequencing, and although sequences were highly degraded. Haplogroups identification was from the sequenced HV1 sections and based on likelihood. Generally site showed a high predominance of Haplotype K(5) followed by H(2) and U(2) haplogroup profiles.
1Eco-anthropologie et Ethnobiologie, UMR 7206 CNRS, MNHN, Univ Paris Diderot, Sorbonne Paris Cité, F-75005, Paris, France, 2Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Leipzig, Germany
1Centre for GeoGenetics. University of Copenhagen, Copenhagen, Denmark, 2Institute of Immunology. Oslo University Hospital. University of Oslo, Oslo, Norway, 3Center for Biological Sequence Analysis. Technical University of Denmark, Kongens Lyngby, Denmark
We have generated genome-wide data for 10 unrelated reputedly non-admixed Easter Islanders. By using non-parametric multidimensional statistics and clustering methods, we show genome-wide patterns consistent with both Native American and European admixture. We infer local Polynesian, Native American and European ancestry tracts and compare their length distributions to those expected under different demographic history models. We find more support for a model with Native American admixture event that predates a European admixture event. By masking the European and Native American ancestry tracts, we reconstruct the recent history of the Easter Island population compared to other existing genotyped Oceanic populations. These results provide additional detailed insight into the demographic history of Polynesian islanders revealing an outstanding event in recent human history.
1Columbia University, New York, NY, USA, 2Yale University, New Haven, CT, USA, 3The Feinstein Institute, Manhasset, NY, USA, 4The Zucker Hillside Hospital, Glen Oaks, NY, USA, 5Icahn School of Medicine at Mount Sinai, New York, NY, USA, 6Albert Einstein College of Medicine, New York, NY, USA, 7Memorial Sloan Kettering Cancer Center, New York, NY, USA, 8The Hebrew University of Jerusalem, Jerusalem, Israel, 9Beth Israel Medical Center, New York, NY, USA
Department of Genetics, Harvard Medical School, Boston, USA
National University of Ireland Galway, Galway, Connaught, Ireland
1Harvard Medical School, Boston, MA, USA, 2Broad Institute of Harvard and MIT, Cambridge, MA, USA, 3Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 4Hartwick College, Oneonta, NY, USA
We applied the SNP capture as well as mitochondrial genome enrichment to a series of 65 bones dating to between 3,000-9,000 years ago from the Samara district of Russia in the far east of Europe, a region that has been suggested to be part of the Proto-Indo-European homeland. We successfully extracted nuclear data from 10-90% of targeted SNPs for more than 40 of the samples, and for all of these samples also obtained complete mitochondrial genomes. We report three key findings:
- Samples from the Samara region possess Ancient North Eurasian (ANE) admixture related to a recently published 24,000 year old Upper Paleolithic Siberian genome. This contrasts with both European agriculturalists and with European hunter-gatherers from Luxembourg and Iberia who had little such ancestry (Lazaridis et al. arXiv.org 2013). This suggests that European steppe groups may have been be implicated in the dispersal of ANE ancestry across Europe where it is currently pervasive.
- The mtDNA composition of the steppe population is primarily West Eurasian, in contrast with northwest Russian samples of this period (Der Sarkissian et al. PLoS Genetics 2013) where an East Eurasian presence is evident.
- Samara experienced major population turnovers over time: early samples (>6000 years) belong primarily to mtDNA haplogroups U4 and U5, typical of European hunter-gatherers but later ones include haplogroups W, H, T, I, K, J.
[Via Greg Cochran.]
Keywords: body mass index; Mendelian randomization; Cardiometabolic
Authors: M. V. Holmes1,2, L. A. Lange3, T. Palmer4, M. B. Lanktree5, IBC BMI Mendelian Randomization Group, E. E. Schadt6, F. W. Asselbergs7,8,2, A. P. Reiner9,10, B. J. Keating1; 1University of Pennsylvania, Philadelphia, PA, United States, 2University College London, London, United Kingdom, 3University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC, United States, 4University of Warwick, Warwick, United Kingdom, 5McMaster University, Hamilton, ON, Canada, 6Mount Sinai School of Medicine, New York, NY, United States, 7University Medical Center Utrecht, Utrecht, Netherlands, 8Durrer Center for Cardiogenetic Research, Utrecht, Netherlands, 9University of Virginia, Charlottesville, VA, United States, 10Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Abstract: Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses using 14 SNPs associated with BMI from a recent discovery analysis to investigate the causal role of BMI with cardiometabolic traits. We used eight population-based cohorts, including 34,538 individuals of European ancestry with 4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD) and 3,813 stroke cases. A genetically-elevated one kg/m2 increase in BMI resulted in higher levels of fasting glucose, insulin, interleukin-6 and systolic blood pressure but reduced levels of HDL-C and LDL-C (values reported in Table). Apart from LDL-C, all causal estimates were directionally concordant to observational estimates. A genetically-elevated one kg/m2 increase in BMI increased odds of T2D but did not affect risk of CHD or stroke. A meta-analysis incorporating published studies with 27,465 CHD events in 219,423 individuals yielded a pooled odds ratio of 1.04 (95%CI: 0.97, 1.12) per 1 kg/m2 increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits, however whether BMI causally impacts on CHD risk requires further evidence.
Keywords: body mass index; whole genome sequencing; association
Authors: E. Zeggini, UK10K consortium; Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
Abstract: Body weight and fat distribution measures are associated with increased risk of cardiometabolic disease. As part of the UK10K study, we have investigated the genetic architecture of anthropometric traits in 3,538 individuals with 6.5x whole genome sequence (WGS) data from the ALSPAC and TwinsUK cohorts. Variants discovered through WGS, along with those from the 1000 Genomes Project (1KGP), were imputed into additional individuals from the ALSPAC and TwinsUK cohorts with GWAS data (total sample size 9,979). We investigated association between anthropometric traits and 8.6 million low frequency and common variants (MAF>0.01). We are in the process of obtaining in silico replication of prioritised signals. In interim replication analysis across ~15,000 samples, 43 out of 66 novel signals for BMI have the same direction of effect in the replication cohorts (p-value=0.0093). We examined the concordance of the direction of effect at established loci for each trait. Out of the 31 established independent loci for BMI that were present in our data, 28 have the same direction of effect (p-value=2.3e-06). For weight, 10 out of 11 known loci (p-value=0.006), and for height 151 out of 172 loci (p-value < 2.2e-16) have the same direction of effect, respectively. We estimated the improvement in genome-wide signal captured relative to those present in HapMap 2, HapMap 3 or 1KGP. We find no appreciable increase in variance explained as density increases, suggesting that the contribution of variants with MAF>0.01 are likely to be well-captured by existing GWAS implementation. Larger sample sizes will be required to refine these estimates.
Keywords: Intellectual Disability; ROH
Authors: I. Gandin1,2, F. Faletra2, M. Carella3, V. Pecile2, G. Ferrero4, E. Belligni4, P. Palumbo3, O. Palumbo3, P. Bosco5, C. Romano5, C. Belcaro1, D. Vozzi2, A. P. d'Adamo1,2; 1University of Trieste, Trieste, Italy, 2IRCCS Burlo Garofolo, Trieste, Italy, 3IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy, 4AO citta' della salute e della scienza, Torino, Italy, 5IRCCS Oasi Maria SS, Troina(EN), Italy.
Abstract: Several recent studies focused on the effect of extended homozygosity on highly complex and polygenic traits where recessive inheritance may play an important role. Since excess of homozygosity might increase the risk for disorders like schizophrenia, Alzheimer disease and autism, we have set out a study to investigate the effect of ROHs on the degree of Intellectual Disability (ID). About 370 unrelated individuals with ID were collected and classified into mild/moderate ID (MM-ID) for IQ ranging from 35-40 to 70-75 and severe/profound ID (SP-ID) for IQ below 35-40. High-density SNP array data were processed with the aim of detecting and analyze ROHs. Since different array platform were used, homozygosity and ROHs mean length were compared in MM-ID vs SP-ID separately in each dataset. Results were then combined for a meta-analysis. Our data revealed an association between the amount of homozygosity and the degree of ID, according to the recent findings on autism (Gamsiz et al., 2013). Accounting for principal components to control population stratification, we tested for ROHs mean length and detected significantly (p < 0.005) longer stretches in SP-ID compared to MM-ID. Weaker association was detected in burden ROH analysis, showing an increase of the percentage of genome covered by ROHs for SP-ID cases. Extent of ROHs seems to contribute to the pathogenesis of ID, suggesting that autosomal recessive variants have a crucial role on the modulation of the severity of ID that still need to be investigated.
Keywords: ADHD; Polygenic scores; Educational attainment
Authors: E. Stergiakouli1, J. Martin2, M. L. Hamshere2, A. Thapar2, D. M. Evans1, N. J. Timpson1, G. Davey Smith1; 1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom, 2MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, United Kingdom.
High levels of ADHD symptoms during childhood carry risk of worse academic performance and can impact on employment and earnings in adulthood. Polygenic score analysis was used to show that common risk alleles for clinical ADHD contribute to the risk of having higher ADHD symptoms in the general population (Martin et al. in press). We have used polygenic score analysis to investigate the contribution of common risk variants for clinical ADHD on educational performance and IQ in the general population.
Academic performance was assessed using results from Key Stage 3 national tests and externally marked GCSE examinations in 6,385 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Polygenic risk scores were calculated for ALSPAC children and their mothers based on the results of an ADHD GWAS (Stergiakouli et al. 2012).
ADHD polygenic scores on the children were associated with worst educational outcomes as represented by both time points and also with lower IQ scores at age 15.5 (see Table). Moreover, ADHD polygenic scores on the mothers were associated with lower IQ in the mothers and worst educational outcomes in the children (see Table).
Our results suggest that the same genetic variants that are relevant for an ADHD diagnosis are also implicated in impaired academic performance in the general population and lower IQ score in both children and adults.
Keywords: mitochondrial DNA; molecular phylogeography; molecular evolution
Authors: B. Malyarchuk1, M. Derenko1, T. Grzybowski2, M. Perkova1, G. Denisova1, A. Litvinov1, U. Rogalla2, K. Skonieczna2; 1Institute of Biological Problems of the North, Magadan, Russian Federation, 2Institute of Forensic Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland.
Abstract: To resolve the phylogeny of some uncommon and poorly studied West Eurasian mitochondrial DNA (mtDNA) haplogroups, we sequenced 32 U2e and 19 U3 complete mitogenomes of Central and Eastern Europeans (Czechs, Slovaks, Poles, Russians, Ukrainians and Belarusians) and re-analysed the available at the present time data on 74 U2e and 80 U3 complete mtDNAs. Molecular dating suggests that the coalescence time estimates are ~21 and ~35 thousand years (ky) for haplogroups U2e and U3, respectively. Detailed analysis of about 500 Slavic complete mitogenomes belonging to different haplogroups allowed us to identify a number of lineages that seem specific for Central and Eastern Europe (U3b1b, U4a2a1, U5a2a1c, U2e1b1a, U2e1b1, U3a1a, H5a1f, U5a1a1a1, U5a1c1, U2e2a1a, U4a2a, H5a2, U2e2a1d and U5a1b1b). These subhaplogroups consist of similar haplotypes revealed in different ethnic groups of modern Slavs, thereby proving the existence of ethnolinguistic community of Slavs through DNA testing. Evolutionary age of Slavic-specific subhaplogroups is calculated to approximately 3.9 ky (from 2.3 to 5.9 ky, according to the mutation rate proposed by Soares et al. (2009) for the entire mtDNA molecule). This indicates that the ancestors of modern Slavs inhabited areas of Central and Eastern Europe from the times of Bronze and Iron Ages, i.e. earlier than it was estimated on the basis of archaeological, historical and linguistic data. This study was supported by Russian Foundation for Basic Research (grant 14-04-00131) and the Program of Presidium of Russian Academy of Sciences (grant 12-I-P30-12).
Keywords: olfactory receptor clusters; Silk Road; population structure
Authors: M. Mezzavilla1,2, S. Ulivi2, P. Gasparini1,2, V. Colonna3; 1University of Trieste, Trieste, Italy, 2Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy, 3Institute of Genetics and Biophysics "A. Buzzati-Traverso", National Research Council (CNR), Napoli, Italy.
Abstract: Smell is a versatile mechanism for recognizing different odours and is mediated by olfactory receptors. While collecting phenotypes related to smell in six countries along the Silk Road, we found an increased rate of failure to discriminate odorants in individuals from Tajikistan respect to the other countries. Using haplotype-based association we linked this to a 15 kb region within olfactory receptor gene cluster on chromosome 6 (p-value 3.86e-05). This region is embedded in the largest intron of OR5V1 and is downstream OR11A1 and upstream OR12D3. We also analysed genetic variability in 1,114 unrelated samples either from the Silk Road and ten other worldwide populations at over 300,000 polymorphic sites and characterized population genetic structure of the Silk Road within a worldwide context with a resolution never obtained before. We identified genetic components peculiar to Central Asia and observed that Tajikistan behaves as an outlier population. Indeed Tajiks share a consistent number of unusually large stretches of homozygosity and have the lowest effective population size (Ne) among the studied populations, most likely as the result of past isolation and/or consanguinity. Altogether these novel findings clarify the complex genetic patterns of the Silk Road populations and suggest that the smell misperception phenotype observed in Tajikistan might be the result of a combination of genetic drift and relaxed selection at the olfactory receptors genes.
Keywords: linear mixed model; genetic correlation
Authors: M. Pirinen1, C. Benner1, T. Lehtimäki2, J. G. Eriksson3,4,5, O. T. Raitakari6,7, M. Järvelin8,9,10, V. Salomaa3, S. Ripatti1,11,12; 1Institute for Molecular Medicine Finland, Helsinki, Finland, 2Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere School of Medicine, Tampere, Finland, 3Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, 4Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, 5Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland, 6Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland, 7Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, 8Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom, 9Institute of Health Sciences, University of Oulu, Oulu, Finland, 10Biocenter Oulu, University of Oulu, Oulu, Finland, 11Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, 12Hjelt Institute, University of Helsinki, Helsinki, Finland.
Abstract: Several modern technologies, such as nuclear magnetic resonance and mass spectrometry platforms in metabolomics, produce high-dimensional phenotype data on individuals. A first step towards utilising high-dimensional phenotypes in genetic studies is to understand how their genetic components are related.
Recent algorithmic advances in multivariate linear mixed models have enabled variance component estimation for pairs of traits using population samples of individuals and genome-wide panels of SNPs. However, current methods have not been tailored for situations where hundreds of traits are available on the same set of individuals. For such settings, we introduce an algorithm that efficiently decomposes pairwise phenotypic correlations into genetic and environmental components.
We illustrate our approach with an application to 105 pairs of metabolic and anthropometric traits measured on up to 14,000 Finnish individuals. For example, we estimate that the observed phenotypic correlation (-0.41) between triglyserides (TG) and HDL cholesterol decomposes into an additive genetic correlation (-0.59, s.e. 0.06) and an environmental correlation (-0.36 s.e. 0.02).
We discuss the interpretation of genetic correlations as correlations between locus-wise genetic effects and characterise settings where prior information about genetic correlation increases statistical power to identify pleiotropic loci, i.e. loci that contribute to multiple traits.
Keywords: SHBG; polymorphism; athletes
Authors: E. S. Egorova1, L. J. Mustafina2, I. I. Ahmetov2,1; 1Kazan State Medical University, Kazan, Russian Federation, 2Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russian Federation.
Abstract: Testosterone regulates muscle mass and strength, bone mass, fat distribution and the production of red blood cells. Sex hormone-binding globulin (SHBG) is the key protein responsible for binding and transporting of testosterone. SHBG regulates its bioavailability and therefore its effects in the body. Polymorphism at the SHBG gene locus (rs12150660 G/T) has been associated with testosterone concentrations. Since individuals with the TT genotype have higher serum testosterone concentrations in comparison with carriers of the G allele (data from GWAS), we hypothesized that the carriage of the T allele may give some advantage for strength and power performance. The aim of the study was to investigate the association between the SHBG G/T polymorphism, athlete status and muscle mass. A total of 363 Russian athletes and 130 controls were genotyped using RT-PCR. Muscle mass was measured by body composition analyzer Tanita MC-980. The frequencies of the T allele in power-oriented athletes (n=143, 20.3%; P=0.7462), endurance-oriented athletes (n=220, 15.0%; P=0.2054) and a whole cohort of athletes (17.1%; P=0.5078) were not significantly different from controls (18.8%). However, the frequency of the T allele in elite power-oriented athletes (n=65, 26.2 vs. 12%, P=0.0061) was significantly higher as compared with elite endurance-oriented athletes (n=58). Furthermore, correlation analysis showed positive association between the T allele and muscle mass among non-elite female athletes (n=8, P=0.0072, r= 0.8729). Although more evidence is needed, one might suggest that the SHBG gene G/T polymorphism is associated with power athlete status.
Title: J17.28 - Genome-wide association analysis identifies a locus on DMD (dystrophin) gene for power athlete status in Russians
Keywords: GWAS; athlete; DMD
Authors: V. A. Naumov1, I. I. Ahmetov2, A. K. Larin1, E. V. Generozov1, N. A. Kulemin1, E. A. Ospanova1, A. V. Pavlenko1, E. S. Kostryukova1, D. G. Alexeev1, V. M. Govorun1; 1Research Institute for Physical-Chemical Medicine, Moscow, Russian Federation, 2Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russian Federation.
Abstract: Power athlete status is a heritable trait: around two-thirds of the variance in this phenotype is explained by genetic factors. Since power and endurance are located at the opposite extremes of a muscle performance continuum, a genome-wide association study (GWAS) of elite Russian power-oriented athletes (sprinters and strength athletes) and endurance-oriented athletes as controls was performed to identify common genetic variants associated with elite power athlete status. 102 sprinters, 86 strength athletes and 178 endurance-oriented athletes were genotyped using the Illumina® HumanOmni1-Quad BeadChips. When comparing sprinters and endurance-oriented athletes, the most significant association (P=6.2[[unable to display character: ∗]]10-7) was shown for the rs939787 polymorphism. Interestingly, this association was replicated (P=2.9[[unable to display character: ∗]]10-6) by comparing strength athletes and endurance-oriented athletes (P=3[[unable to display character: ∗]]10-8 when sprinters and strength athletes were combined). The rs939787 is located in the DMD (dystrophin) gene which plays an important role in muscle contraction and strength, linking the intracellular cytoskeleton to the extracellular matrix. In conclusion, our data suggest that the DMD gene rs939787 polymorphism is associated with elite power athlete status in Russians.
Title: J17.58 - Variations in nuclear genes are associated with elite sport performance in the Polish population
Keywords: sport performance; ACE; ACTN3
Authors: B. J. Peplonska1, K. Safranow2, J. G. Adamczyk3, M. Siewierski3, H. Sozański3, A. K. Gajewski3, M. Berdynski1, A. Maruszak1, C. Zekanowski3; 1Mossakowski Medical Research Centre Polish Academy of Sciences, Warszawa, Poland, 2Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland, 3Department of Sport’s Theory, Institute of Sport, Jozef Pilsudski University oh Physical Education in Warsaw, Warszawa, Poland.
Abstract: Objectives: Single nucleotide polymorphisms are the most common type of human genetic variation. It is widely recognized that genetic factors located in mitochondrial and nuclear genomes influence sport performance. The aim of our study was to assess whether selected nuclear DNA variants are associated with athlete performance in the Polish population.
Methods: The study group comprised 413 unrelated elite athletes and the control group consisted of 451unrelated sedentary individuals. The athletes were stratified into two subgroups: the power athletes (n=188) and the endurance ones (n=225). The study group included 284 participants of Olympic and International Games and the remaining 129 athletes were national[[unable to display character: –]]level athletes. The DNA was isolated from peripheral blood lymphocytes using standard procedures. Genotyping of 10 nuclear DNA variants (ACE, rs4341; ACTN3, rs1815739; GABPB1, rs12594956; CHRNB3, rs4950; AGT, rs699; FAAH, rs324420; PPARG, rs1801282; TFAM, rs1937; TFAM, rs 2306604; PGC1α, rs 8192678) was conducted using TaqMan method. All statistical analyses were performed using Statistica ver. 10.
Results: We showed that six polymorphisms were associated with outstanding results in power (TFAM,rs 2306604, FAAH, ACE, ACTN3) or endurance sports (CHRNB3, GABP1). Gender and sport level of athletes were also significant
Conclusion: Our study indicates that in the Polish population genetic background could influence sport performance.
Title: J17.48 - The association of REN gene polymorphism with athlete status and muscle mass
Keywords: polymorphism; REN gene; skeletal muscle
Authors: L. J. Mustafina1,2, G. N. Khafizova1, R. R. Almetova1, R. R. Kasimova1, E. S. Egorova2, I. I. Ahmetov1,2; 1Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russian Federation, 2Kazan State Medical University, Kazan, Russian Federation.
Abstract: The renin-angiotensin system (RAS) is supposed to be one of the regulators of skeletal muscle growth and differentiation (Zhang et al. 2003; Johnston et al. 2011). Renin (encoded by REN gene), as a component of the RAS, activates the renin-angiotensin cascade by catalyzing the conversion of angiotensinogen to angiotensin I (Rupert, 2006). The aim of present study was to investigate the association between the intron 8 83A/G (rs2368564) polymorphism of the REN gene, athlete status and muscle mass in Russians. Two hundred and sixty eight Russian athletes (90 females and 178 males) from different sporting disciplines were involved in the study. REN genotype and allele frequencies were compared to 151 controls (74 females and 77 males). Genotyping for the REN polymorphism was performed by RT-PCR. Muscle mass parameters were assessed by bioelectrical impedance analyzer Tanita MC 980 (Japan) in 125 athletes (44 females and 81 males). We found that the frequency of the REN G allele was significantly higher in power-oriented athletes (78 vs 68%; P=0.021) compared to controls and this difference was even more pronounced in elite power-oriented athletes (89%; P=0.018). Furthermore, the REN G allele was positively correlated with fat-free mass, absolute muscle mass, muscle mass of trunk and left/right legs in elite athletes. In conclusion, we have shown that the 83A/G polymorphism of the REN gene is associated with power athlete status and skeletal muscle parameters in Russians.
Keywords: Genetic introgression; Principal Component Analysis; GS:SFHS
Authors: C. Amador1, J. Huffman1, H. Trochet1, A. Campbell1, D. Porteous1, G. Scotland1, N. Hastie1, V. Vitart1, C. Hayward1, P. Navarro1, C. S. Haley1,2; 1MRC IGMM, University of Edinburgh, Edinburgh, United Kingdom, 2Roslin Institute and Royal (Dick) School of Veterinary Studies, Edinburgh, United Kingdom.
Abstract: Generation Scotland’s Scottish Family Health Study (GS:SFHS) includes over 24,000 participants from across Scotland with records for health-related traits and environmental covariates, 10,000 genotyped for ~700K SNPs. The cohort represents an important resource for the study of complex traits and diseases. We have analysed the genomic structure of GS:SFHS as a preliminary step towards choosing appropriate subsets of individuals and statistical techniques for future studies. Initially we merged the GS:SFHS data with 1092 individuals of diverse ancestries from the 1000 Genomes project and estimated genomic relationships using the ~700K SNPs. A Principal Component Analysis on the resulting relationships facilitated identification of a group of 70 individuals of likely Italian ancestry and a number of individuals with African or Asian ancestry. We characterised the amount of genetic introgression and were able to differentiate between individuals with a few small exogenous regions in their genome, and those with long exogenous haplotypes covering a large part of the genome. We found that the pattern of homozygosity was very similar to that of other European populations and identified an individual carrying a chromosome 1 uniparental disomy. Overall, there is very limited evidence for geographic differentiation or stratification of the GS:SFHS sample within Scotland. These findings provide a genomic perspective on the history of the Scottish population, and have implications for further analyses, such as studying the contributions of common and rare variants to trait heritabilities and evaluation of genomic and phenotypic prediction of disease.
Title: P16.66-M - The influence of genetics on personality development
Keywords: Personality; NEO-FFI Authors: K. B. Wolffhechel1, H. Jarmer1, S. M. van den Berg2, M. H. M. de Moor3, D. I. Boomsma3; 1Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark, 2Department of Research Methodology, Measurement and Data Analysis, University of Twente, Enschede, Netherlands, 3Department of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands.
Abstract: Personality is known as hereditary to a certain extent. In this work we attempt to classify personality traits as binary traits based on genetic information only. For this we used the 60-item NEO-FFI and over 8 million SNPs from 6655 Dutch participants. For feature selection we performed a genome-wide association for each personality trait in a five-fold cross validation setup. All SNPs with a p-value < 0.01 were chosen as predictors for a given fold and a given personality trait, amounting to approximately 2,500 associated SNPs for each trait. An artificial neural network was trained with the SNPs as input and the personality scores as output. We found it possible to classify a person’s personality to the two sides of the scale significantly better than random. The results of this study prove in a novel way that genetics have an influence on personality. The next step is to identify, which genes these SNPs belong to, which hopefully will lead to a greater understanding of the processes involved in personality development and the onset of personality disorders.
Abstract: Personality traits are thought to be endophenotypes (high Harm Avoidance (HA), low Self-directedness (SD)) for most psychiatric disorders and predictors of life outcomes. Genetic influences on personality traits are attributable to many genes of small effect and are modulated by environmental factors. We aimed to examine gene-environment (GxE) and gene-gene (GxG) interaction models based on neurotrophic factor (NGF, BDNF, NTRK2, NTRK3), serotoninergic (SLC6A4, TPH1) and dopaminergic system (DRD2, SLC6A3) gene polymorphisms contributing into personality traits variation in healthy individuals.
In total, 1018 healthy individuals (68% women) from Russia (mean age±SD: 19.81±2.65 years) without any history of psychopathologies were subjected to personality traits assessment via TCI-125 (Cloninger et al., 1993). Involved individuals are Caucasians from Russian (N=409), Tatar (N=290), Bashkir (N=130) and Udmurt populations (N=189). Socio-demographic data including gender, ethnicity, order and season of birth (SOB), place of residence, level of income, childhood maltreatment were obtained. Genotyping of 70 SNPs was performed with SNPlexTM platform (Applied Biosystems). Statistical analysis was conducted with PLINK v.1.07 corrected via FDR-procedure for multiple comparisons.
The present study revealed GxE models demonstrated BDNF Val66Met*SOB (PFDR=0.036), BDNF rs1519479*ethnicity (PFDR=0.042) and 5-HTTLPR*SOB (PFDR=0.05) interactions affected HA. Moreover, variations in SD were caused by interactions between BDNF Val66Met (PFDR=0.048), BDNF rs2030323 (PFDR=0.035) and ethnicity. Accordingly, genetic testing for BDNF and 5-HTT gene polymorphisms assuming gender, ethnicity and SOB confounding is necessary for psychopathologies prevention at early stages. This work was supported by Russian foundation for humanities grant 13-06-00583a.