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

Pankratov, Vasili, Mezzavilla, Massimo, Aneli, Serena, Kuznetsov, Ivan A., Fusco, Daniela, Wilson, James F., Metspalu, Mait, Provero, Paolo, Pagani, Luca, Marnetto, Davide·2024·European Journal of Human Genetics
DOI 10.1038/s41431-024-01678-9PMC PMC11576899

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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.

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Metadata

Authors
Pankratov, V., Mezzavilla, M., Aneli, S., Kuznetsov, I. A., Fusco, D., Wilson, J. F., Metspalu, M., Provero, P., Pagani, L., & Marnetto, D.
ORCID
Venue
European Journal of Human Genetics
Publisher
Springer Science and Business Media LLC
Published
2024-08-10
Volume
32
Issue
11
Pages
1492-1499
ISSN
  • 1018-4813
  • 1476-5438
DOI
10.1038/s41431-024-01678-9
PMC
PMC11576899
Cited by
10
References
12
Language
en
Licence
Funders
  • Università degli Studi di Torino (Grant For Internationalization 2022)
  • EC | Horizon 2020 Framework Programme (810645)
  • EC | European Regional Development Fund (MOBEC008)
  • Eesti Teadusagentuur (PRG1899)

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