Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks.

Autor: Pankratov V; Center for Genomics, Evolution and Medicine, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia. vasili.pankratov@ut.ee., Mezzavilla M; Department of Biology, University of Padua, Padua, Italy., Aneli S; Department of Public Health Sciences and Pediatrics, University of Turin, 10126, Turin, Italy., Kuznetsov IA; Center for Genomics, Evolution and Medicine, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia., Fusco D; Department of Neurosciences, University of Turin, 10126, Turin, Italy., Wilson JF; Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland.; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland., Metspalu M; Institute of Genomics, University of Tartu, 51010, Tartu, Estonia., Provero P; Department of Neurosciences, University of Turin, 10126, Turin, Italy.; Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy., Pagani L; Department of Biology, University of Padua, Padua, Italy.; Institute of Genomics, University of Tartu, 51010, Tartu, Estonia., Marnetto D; Department of Neurosciences, University of Turin, 10126, Turin, Italy. davide.marnetto@unito.it.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2024 Aug 10. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1038/s41431-024-01678-9
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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