Vasili Pankratov, Massimo Mezzavilla, Serena Aneli, Ivan A. Kuznetsov, Daniela Fusco, James F. Wilson, Mait Metspalu, Paolo Provero, Luca Pagani, Davide Marnetto
{"title":"在欧洲生物库中,祖先遗传成分与复杂的性状景观始终相关。","authors":"Vasili Pankratov, Massimo Mezzavilla, Serena Aneli, Ivan A. Kuznetsov, Daniela Fusco, James F. Wilson, Mait Metspalu, Paolo Provero, Luca Pagani, Davide Marnetto","doi":"10.1038/s41431-024-01678-9","DOIUrl":null,"url":null,"abstract":"The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":"32 11","pages":"1492-1499"},"PeriodicalIF":3.7000,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41431-024-01678-9.pdf","citationCount":"0","resultStr":"{\"title\":\"Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks\",\"authors\":\"Vasili Pankratov, Massimo Mezzavilla, Serena Aneli, Ivan A. Kuznetsov, Daniela Fusco, James F. Wilson, Mait Metspalu, Paolo Provero, Luca Pagani, Davide Marnetto\",\"doi\":\"10.1038/s41431-024-01678-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.\",\"PeriodicalId\":12016,\"journal\":{\"name\":\"European Journal of Human Genetics\",\"volume\":\"32 11\",\"pages\":\"1492-1499\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-08-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41431-024-01678-9.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Human Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s41431-024-01678-9\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41431-024-01678-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks
The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.
期刊介绍:
The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community.
Key areas include:
-Monogenic and multifactorial disorders
-Development and malformation
-Hereditary cancer
-Medical Genomics
-Gene mapping and functional studies
-Genotype-phenotype correlations
-Genetic variation and genome diversity
-Statistical and computational genetics
-Bioinformatics
-Advances in diagnostics
-Therapy and prevention
-Animal models
-Genetic services
-Community genetics