TY - JOUR T1 - Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. JF - Nat Commun Y1 - 2018 A1 - Wyss, Annah B A1 - Sofer, Tamar A1 - Lee, Mi Kyeong A1 - Terzikhan, Natalie A1 - Nguyen, Jennifer N A1 - Lahousse, Lies A1 - Latourelle, Jeanne C A1 - Smith, Albert Vernon A1 - Bartz, Traci M A1 - Feitosa, Mary F A1 - Gao, Wei A1 - Ahluwalia, Tarunveer S A1 - Tang, Wenbo A1 - Oldmeadow, Christopher A1 - Duan, Qing A1 - de Jong, Kim A1 - Wojczynski, Mary K A1 - Wang, Xin-Qun A1 - Noordam, Raymond A1 - Hartwig, Fernando Pires A1 - Jackson, Victoria E A1 - Wang, Tianyuan A1 - Obeidat, Ma'en A1 - Hobbs, Brian D A1 - Huan, Tianxiao A1 - Gui, Hongsheng A1 - Parker, Margaret M A1 - Hu, Donglei A1 - Mogil, Lauren S A1 - Kichaev, Gleb A1 - Jin, Jianping A1 - Graff, Mariaelisa A1 - Harris, Tamara B A1 - Kalhan, Ravi A1 - Heckbert, Susan R A1 - Paternoster, Lavinia A1 - Burkart, Kristin M A1 - Liu, Yongmei A1 - Holliday, Elizabeth G A1 - Wilson, James G A1 - Vonk, Judith M A1 - Sanders, Jason L A1 - Barr, R Graham A1 - de Mutsert, Renée A1 - Menezes, Ana Maria Baptista A1 - Adams, Hieab H H A1 - van den Berge, Maarten A1 - Joehanes, Roby A1 - Levin, Albert M A1 - Liberto, Jennifer A1 - Launer, Lenore J A1 - Morrison, Alanna C A1 - Sitlani, Colleen M A1 - Celedón, Juan C A1 - Kritchevsky, Stephen B A1 - Scott, Rodney J A1 - Christensen, Kaare A1 - Rotter, Jerome I A1 - Bonten, Tobias N A1 - Wehrmeister, Fernando César A1 - Bossé, Yohan A1 - Xiao, Shujie A1 - Oh, Sam A1 - Franceschini, Nora A1 - Brody, Jennifer A A1 - Kaplan, Robert C A1 - Lohman, Kurt A1 - McEvoy, Mark A1 - Province, Michael A A1 - Rosendaal, Frits R A1 - Taylor, Kent D A1 - Nickle, David C A1 - Williams, L Keoki A1 - Burchard, Esteban G A1 - Wheeler, Heather E A1 - Sin, Don D A1 - Gudnason, Vilmundur A1 - North, Kari E A1 - Fornage, Myriam A1 - Psaty, Bruce M A1 - Myers, Richard H A1 - O'Connor, George A1 - Hansen, Torben A1 - Laurie, Cathy C A1 - Cassano, Patricia A A1 - Sung, Joohon A1 - Kim, Woo Jin A1 - Attia, John R A1 - Lange, Leslie A1 - Boezen, H Marike A1 - Thyagarajan, Bharat A1 - Rich, Stephen S A1 - Mook-Kanamori, Dennis O A1 - Horta, Bernardo Lessa A1 - Uitterlinden, André G A1 - Im, Hae Kyung A1 - Cho, Michael H A1 - Brusselle, Guy G A1 - Gharib, Sina A A1 - Dupuis, Josée A1 - Manichaikul, Ani A1 - London, Stephanie J AB -

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 = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

VL - 9 IS - 1 ER -