Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Authors:
Sina A Gharib, MD
Sina A Gharib, MD
Center for Lung Biology, UW Medicine Sleep Center, University of Washington
Associate Professor
Seattle, WA | United States
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 Hongsheng Gui Margaret M Parker Donglei Hu Lauren S Mogil 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 L Sanders R Graham Barr Renée de Mutsert Ana Maria Baptista Menezes Hieab H H Adams Maarten van den Berge Roby Joehanes Albert M Levin Jennifer Liberto 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 Shujie Xiao Sam Oh Nora Franceschini Jennifer A Brody Robert C Kaplan Kurt Lohman Mark McEvoy Michael A Province Frits R Rosendaal Kent D Taylor David C Nickle L Keoki Williams Esteban G Burchard Heather E Wheeler Don D Sin Vilmundur Gudnason Kari E North Myriam Fornage Bruce M Psaty Richard H Myers George O'Connor Torben Hansen Cathy C Laurie Patricia A 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 Hae Kyung Im Michael H Cho Guy G Brusselle Josée Dupuis Ani Manichaikul Stephanie J London

Nat Commun 2018 07 30;9(1):2976. Epub 2018 Jul 30.

Epidemiology Branch National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, NC, 27709, USA.

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.

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http://dx.doi.org/10.1038/s41467-018-05369-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065313PMC
July 2018
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