| Literature DB >> 32888493 |
Ming-Huei Chen1, Laura M Raffield2, Abdou Mousas3, Saori Sakaue4, Jennifer E Huffman5, Arden Moscati6, Bhavi Trivedi7, Tao Jiang8, Parsa Akbari9, Dragana Vuckovic10, Erik L Bao11, Xue Zhong12, Regina Manansala13, Véronique Laplante14, Minhui Chen15, Ken Sin Lo3, Huijun Qian16, Caleb A Lareau11, Mélissa Beaudoin3, Karen A Hunt7, Masato Akiyama17, Traci M Bartz18, Yoav Ben-Shlomo19, Andrew Beswick20, Jette Bork-Jensen21, Erwin P Bottinger22, Jennifer A Brody23, Frank J A van Rooij24, Kumaraswamynaidu Chitrala25, Kelly Cho26, Hélène Choquet27, Adolfo Correa28, John Danesh29, Emanuele Di Angelantonio30, Niki Dimou31, Jingzhong Ding32, Paul Elliott33, Tõnu Esko34, Michele K Evans25, James S Floyd35, Linda Broer36, Niels Grarup21, Michael H Guo37, Andreas Greinacher38, Jeff Haessler39, Torben Hansen21, Joanna M M Howson40, Qin Qin Huang10, Wei Huang41, Eric Jorgenson27, Tim Kacprowski42, Mika Kähönen43, Yoichiro Kamatani44, Masahiro Kanai45, Savita Karthikeyan8, Fotis Koskeridis46, Leslie A Lange47, Terho Lehtimäki48, Markus M Lerch49, Allan Linneberg50, Yongmei Liu51, Leo-Pekka Lyytikäinen48, Ani Manichaikul52, Hilary C Martin10, Koichi Matsuda53, Karen L Mohlke2, Nina Mononen48, Yoshinori Murakami54, Girish N Nadkarni6, Matthias Nauck55, Kjell Nikus56, Willem H Ouwehand57, Nathan Pankratz58, Oluf Pedersen21, Michael Preuss6, Bruce M Psaty59, Olli T Raitakari60, David J Roberts61, Stephen S Rich52, Benjamin A T Rodriguez1, Jonathan D Rosen62, Jerome I Rotter63, Petra Schubert5, Cassandra N Spracklen64, Praveen Surendran65, Hua Tang66, Jean-Claude Tardif67, Richard C Trembath68, Mohsen Ghanbari69, Uwe Völker70, Henry Völzke71, Nicholas A Watkins72, Alan B Zonderman25, Peter W F Wilson73, Yun Li74, Adam S Butterworth75, Jean-François Gauchat14, Charleston W K Chiang76, Bingshan Li77, Ruth J F Loos6, William J Astle78, Evangelos Evangelou79, David A van Heel7, Vijay G Sankaran11, Yukinori Okada80, Nicole Soranzo81, Andrew D Johnson1, Alexander P Reiner82, Paul L Auer83, Guillaume Lettre84.
Abstract
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.Entities:
Keywords: interleukin-7, genetic architecture, fine-mapping, selective sweeps, polygenic trait score, phenome-wide association study
Mesh：
Substances：
Year: 2020 PMID： 32888493 PMCID： PMC7480402 DOI： 10.1016/j.cell.2020.06.045
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850