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Saunders, G.R.B.* ; Wang, X.* ; Chen, F.* ; Jang, S.K.* ; Liu, M.* ; Wang, C.* ; Gao, S.* ; Jiang, Y.* ; Khunsriraksakul, C.* ; Otto, J.M.* ; Addison, C.* ; Akiyama, M.* ; Albert, C.M.* ; Aliev, F.* ; Alonso, A.* ; Arnett, D.K.* ; Ashley-Koch, A.E.* ; Ashrani, A.A.* ; Barnes, K.C.* ; Barr, R.G.* ; Bartz, T.M.* ; Becker, D.M.* ; Bielak, L.F.* ; Benjamin, E.J.* ; Bis, J.C.* ; Bjornsdottir, G.* ; Blangero, J.* ; Bleecker, E.R.* ; Boardman, J.D.* ; Boerwinkle, E.* ; Boomsma, D.I.* ; Boorgula, M.P.* ; Bowden, D.W.* ; Brody, J.A.* ; Cade, B.E.* ; Chasman, D.I.* ; Chavan, S.* ; Chen, Y.D.I.* ; Chen, Z.* ; Cheng, I.* ; Cho, M.H.* ; Choquet, H.* ; Cole, J.W.* ; Cornelis, M.C.* ; Cucca, F.* ; Curran, J.E.* ; de Andrade, M.* ; Dick, D.M.* ; Docherty, A.R.* ; Duggirala, R.* ; Eaton, C.B.* ; Ehringer, M.A.* ; Esko, T.* ; Faul, J.D.* ; Silva, L.F.D.* ; Fiorillo, E.* ; Fornage, M.* ; Freedman, B.I.* ; Gabrielsen, M.E.* ; Garrett, M.E.* ; Gharib, S.A.* ; Gieger, C. ; Gillespie, N.A.* ; Glahn, D.C.* ; Gordon, S.D.* ; Gu, C.C.* ; Gu, D.* ; Gudbjartsson, D.F.* ; Guo, X.* ; Haessler, J.* ; Hall, M.E.* ; Haller, T.* ; Harris, K.M.* ; He, J.* ; Herd, P.* ; Hewitt, J.K.* ; Hickie, I.B.* ; Hidalgo, B.* ; Hokanson, J.E.* ; Hopfer, C.J.* ; Hottenga, J.J.* ; Hou, L.* ; Huang, H.* ; Hung, Y.J.* ; Hunter, D.J.* ; Hveem, K.* ; Hwang, S.J.* ; Hwu, C.M.* ; Iacono, W.G.* ; Irvin, M.R.* ; Jee, Y.H.* ; Johnson, E.O.* ; Joo, Y.Y.* ; Jorgenson, E.* ; Justice, A.E.* ; Kamatani, Y.* ; Kaplan, R.C.* ; Kaprio, J.* ; Kardia, S.L.R.* ; Keller, M.C.* ; Peters, A. ; Peyser, P.A.* ; Polderman, T.J.C.* ; Redline, S.* ; Reiner, A.P.* ; Rice, J.P.* ; Rich, S.S.* ; Richmond, N.E.* ; Schwartz, D.A.* ; Shadyab, A.H.* ; Sicinski, K.* ; Sotoodehnia, N.* ; Stallings, M.C.* ; Stefánsson, H.* ; Sun, X.* ; Tal-Singer, R.* ; Taylor, K.D.* ; Turman, C.* ; Tyrfingsson, T.* ; Wall, T.L.* ; Walters, R.G.* ; Weiss, S.T.* ; Whitfield, J.B.* ; Wiggins, K.L.* ; Willemsen, G.* ; Winsvold, B.S.* ; Yanek, L.R.* ; Zhao, W.* ; Zöllner, S.* ; Zuccolo, L.* ; Batini, C.* ; Bergen, A.W.* ; Bierut, L.J.* ; David, S.P.* ; Gagliano Taliun, S.A.* ; Hancock, D.B.* ; Munafò, M.R.* ; Thorgeirsson, T.E.* ; Liu, D.J.* ; Vrieze, S.*

Genetic diversity fuels gene discovery for tobacco and alcohol use.

Nature 612, 720–724 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Neurotrophic Factors; Disease; Prediction; Protein; Model
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 612, Issue: 7941, Pages: 720–724 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Grants NIAAA NIH HHS
NHLBI NIH HHS