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Stæger, F.F.* ; Andersen, M.K.* ; Li, Z.* ; Hjerresen, J.P.* ; He, S.* ; Santander, C.G.* ; Jensen, R.T.* ; Rex, K.F.* ; Thuesen, A.C.B.* ; Hanghøj, K.* ; Seiding, I.H.* ; Jørsboe, E.* ; Stinson, S.E.* ; Rasmussen, M.S.* ; Balboa, R.F.* ; Larsen, C.V.L.* ; Bjerregaard, P.* ; Schubert, M.* ; Meisner, J.* ; Linneberg, A.* ; Grarup, N.* ; Zeggini, E. ; Nielsen, R.* ; Jørgensen, M.E.* ; Hansen, T.* ; Moltke, I.* ; Albrechtsen, A.*

Genetic architecture in Greenland is shaped by demography, structure and selection.

Nature 639, 404-410 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Greenlandic Inuit and other indigenous populations are underrepresented in genetic research1,2, leading to inequity in healthcare opportunities. To address this, we performed analyses of sequenced or imputed genomes of 5,996 Greenlanders with extensive phenotypes. We quantified their historical population bottleneck and how it has shaped their genetic architecture to have fewer, but more common, variable sites. Consequently, we find twice as many high-impact genome-wide associations to metabolic traits in Greenland compared with Europe. We infer that the high-impact variants arose after the population split from Native Americans and thus are Arctic-specific, and show that some of them are common due to not only genetic drift but also selection. We also find that European-derived polygenic scores for metabolic traits are only half as accurate in Greenlanders as in Europeans, and that adding Arctic-specific variants improves the overall accuracy to the same level as in Europeans. Similarly, lack of representation in public genetic databases makes genetic clinical screening harder in Greenlandic Inuit, but inclusion of Greenlandic data remedies this by reducing the number of non-causal candidate variants by sixfold. Finally, we identify pronounced genetic fine structure that explains differences in prevalence of monogenic diseases in Greenland and, together with recent changes in mobility, leads to a predicted future reduction in risk for certain recessive diseases. These results illustrate how including data from Greenlanders can greatly reduce inequity in genomic-based healthcare.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Diversity; Genomes; Common; Inuit; Sequence; Variant; Association; Efficient; Ancestry; Insights
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 639, Heft: 8054, Seiten: 404-410 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)
Förderungen European Research Council
Independent Research Fund Denmark
Villum Young Investigator grant
Novo Nordisk Foundation
Steno Diabetes Center Greenland
Novo Nordisk Foundation Centre for Basic Metabolic Research