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Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

2020; Cell Press; Volume: 182; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2020.06.045

1097-4172

Ming‐Huei Chen, Laura M. Raffield, Abdou Mousas, Saori Sakaue, Jennifer E. Huffman, Arden Moscati, Bhavi Trivedi, Tao Jiang, Parsa Akbari, Dragana Vuckovic, Erik L. Bao, Xue Zhong, Regina Manansala, Véronique Laplante, Minhui Chen, Ken Sin Lo, Huijun Qian, Caleb A. Lareau, Mélissa Beaudoin, Karen A. Hunt, Masato Akiyama, Traci M. Bartz, Yoav Ben‐Shlomo, Andrew D Beswick, Jette Bork‐Jensen, Erwin P. Böttinger, Jennifer A. Brody, Frank J.A. van Rooij, Kumaraswamy Naidu 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, Qin Huang, Wei Huang, Eric Jorgenson, Tim Kacprowski, Mika Kähönen, Yoichiro Kamatani, Masahiro Kanai, Savita Karthikeyan, Fotios Koskeridis, Leslie A. Lange, Terho Lehtimäki, Markus M. Lerch, Allan Linneberg, Yongmei Liu, Leo‐Pekka Lyytikäinen, Ani Manichaikul, Hilary C. Martin, 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, Blanca Rodríguez, Jonathan D. Rosen, Jerome I. Rotter, Petra Schubert, Cassandra N. Spracklen, Praveen Surendran, Hua Tang, Jean‐Claude Tardif, Richard C. Trembath, Mohsen Ghanbari, Uwe Völker, Henry Völzke, Nicholas A. Watkins, Alan B. Zonderman, Peter W.F. Wilson, Yun Li, Adam S. Butterworth, Jean‐François Gauchat, Charleston W. K. Chiang, Bingshan Li, Ruth J. F. Loos, William J. Astle, Εvangelos Εvangelou, David A. van Heel, Vijay G. Sankaran, Yukinori Okada, Nicole Soranzo, Andrew D. Johnson, Alexander P. Reiner, Paul L. Auer, Guillaume Lettre,

Cancer-related molecular mechanisms research

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 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 EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect 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.