Trans-ethnic and ancestry-specific blood-cell genetics in 746,667 individuals from 5 global populations
By
Ming-Huei Chen,
Laura M Raffield,
Abdou Mousas,
Saori Sakaue,
Jennifer E. Huffman,
Tao Jiang,
Parsa Akbari,
Dragana Vuckovic,
Erik L. Bao,
Arden Moscati,
Xue Zhong,
Regina Manansala,
Véronique Laplante,
Minhui Chen,
Ken Sin Lo,
Huijun Qian,
Caleb A. Lareau,
Mélissa Beaudoin,
Masato Akiyama,
Traci M Bartz,
Yoav Ben-Shlomo,
Andrew Beswick,
Jette Bork-Jensen,
Erwin P. Bottinger,
Jennifer A Brody,
Frank JA van Rooij,
Kumaraswamynaidu Chitrala,
Kelly Cho,
Hélène Choquet,
Adolfo Correa,
John Danesh,
Emanuele Di Angelantonio,
Niki Dimou,
Jingzhong Ding,
Paul Elliott,
Tõnu Esko,
Michele K. Evans,
James S Floyd,
Linda Broer,
Niels Grarup,
Michael H Guo,
Andreas Greinacher,
Jeff Haessler,
Torben Hansen,
Joanna M M Howson,
Wei Huang,
Eric Jorgenson,
Tim Kacprowski,
Mika Kähönen,
Yoichiro Kamatani,
Masahiro Kanai,
Savita Karthikeyan,
Fotis Koskeridis,
Leslie A Lange,
Terho Lehtimäki,
Markus M. Lerch,
Allan Linneberg,
Yongmei Liu,
Leo-Pekka Lyytikäinen,
Ani Manichaikul,
Koichi Matsuda,
Karen L. Mohlke,
Nina Mononen,
Yoshinori Murakami,
Girish N. Nadkarni,
Matthias Nauck,
Kjell Nikus,
Willem H Ouwehand,
Nathan Pankratz,
Oluf Pedersen,
Michael Preuss,
Bruce M. Psaty,
Olli T Raitakari,
David J. Roberts,
Stephen S. Rich,
Benjamin A.T. Rodriguez,
Jonathan D. Rosen,
Jerome I. Rotter,
Petra Schubert,
Cassandra N. Spracklen,
Praveen Surendran,
Hua Tang,
Jean-Claude Tardif,
Mohsen Ghanbari,
Uwe Völker,
Henry Völzke,
Nicholas A Watkins,
Alan B Zonderman,
VA Million Veteran Program,
Peter WF Wilson,
Yun Li,
Adam Butterworth,
Jean-François Gauchat,
Charleston W.K. Chiang,
Bingshan Li,
Ruth J.F. Loos,
William J. Astle,
Evangelos Evangelou,
Vijay G. Sankaran,
Yukinori Okada,
Nicole Soranzo,
Andrew D. Johnson,
Alexander P. Reiner,
Paul L. Auer,
Guillaume Lettre
Posted 18 Jan 2020
bioRxiv DOI: 10.1101/2020.01.17.910497
Most loci identified by GWAS have been found in populations of European ancestry (EA). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EA individuals, we identified 5,552 trait-variant associations at P<5x10-9, including 71 novel loci not found in EA populations. We also identified novel ancestry-specific variants not found in EA, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional, and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EA-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations, and compared genetic architecture and the impact of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
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