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Multiethnic Meta-analysis Identifies New Loci for Pulmonary Function

By Annah B. Wyss, Tamar Sofer, Mi Kyeong Lee, Natalie Terzikhan, Jennifer N. Nguyen, Lies Lahousse, Jeanne C. Latourelle, Albert Vernon Smith, Traci M Bartz, Mary F. Feitosa, Wei Gao, Tarunveer S. Ahluwalia, Wenbo Tang, Christopher Oldmeadow, Qing Duan, Kim de Jong, Mary K. Wojczynski, Xin-Qun Wang, Raymond Noordam, Fernando Pires Hartwig, Victoria E Jackson, Tianyuan Wang, Ma’en Obeidat, Brian D. Hobbs, Tianxiao Huan, Gleb Kichaev, Jianping Jin, Mariaelisa Graff, Tamara B. Harris, Ravi Kalhan, Susan R Heckbert, Lavinia Paternoster, Kristin M. Burkart, Yongmei Liu, Elizabeth G. Holliday, James G Wilson, Judith M. Vonk, Jason Sanders, R. Graham Barr, Renée de Mutsert, Ana Maria Baptista Menezes, Hieab H. H. Adams, Maarten van den Berge, Roby Joehanes, Lenore J Launer, Alanna C. Morrison, Colleen M. Sitlani, Juan C. Celedón, Stephen B. Kritchevsky, Rodney J. Scott, Kaare Christensen, Jerome I Rotter, Tobias N. Bonten, Fernando César Wehrmeister, Yohan Bossé, Nora Franceschini, Jennifer A Brody, Robert C. Kaplan, Kurt Lohman, Mark McEvoy, Michael A Province, Frits R Rosendaal, Kent D Taylor, David C Nickle, Kari E. North, Myriam Fornage, Bruce M Psaty, Richard H. Myers, George O’Connor, Torben Hansen, Cathy C. Laurie, Pat Cassano, Joohon Sung, Woo Jin Kim, John R. Attia, Leslie Lange, H. Marike Boezen, Bharat Thyagarajan, Stephen S Rich, Dennis O. Mook-Kanamori, Bernardo Lessa Horta, André G. Uitterlinden, Don D. Sin, Hae Kyung Im, Michael H Cho, Guy G. Brusselle, Sina A. Gharib, Josée Dupuis, Ani Manichaikul, Stephanie J. London

Posted 05 Oct 2017
bioRxiv DOI: 10.1101/196048 (published DOI: 10.1038/s41467-018-05369-0)

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), African (N=8,429), Asian (N=9,959), and Hispanic/Latino (N=11,775) ethnicities. We identified over 50 novel loci at genome-wide significance in ancestry-specific and/or multiethnic meta-analyses. Recent fine mapping methods incorporating functional annotation, gene expression, and/or differences in linkage disequilibrium between ethnicities identified potential causal variants and genes at known and newly identified loci. Sixteen of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.

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