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

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 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 Mutsert, Ana Maria Baptista Menezes, Hieab H. H. Adams, Maarten 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, Sina A. Gharib, Josée Dupuis, Ani Manichaikul and Stephanie J. London ()
Additional contact information
Annah B. Wyss: US Department of Health and Human Services
Tamar Sofer: Brigham and Women’s Hospital
Mi Kyeong Lee: US Department of Health and Human Services
Natalie Terzikhan: Ghent University Hospital
Jennifer N. Nguyen: University of Virginia
Lies Lahousse: Erasmus University Medical Center
Jeanne C. Latourelle: Boston University School of Medicine
Albert Vernon Smith: Icelandic Heart Association
Traci M. Bartz: University of Washington
Mary F. Feitosa: Washington University School of Medicine
Wei Gao: Boston University School of Public Health
Tarunveer S. Ahluwalia: Metabolic Genetics Section, Faculty of Health and Medical Sciences, University of Copenhagen
Wenbo Tang: Cornell University
Christopher Oldmeadow: Hunter Medical Research Institute and Faculty of Health, University of Newcastle
Qing Duan: University of North Carolina
Kim Jong: University of Groningen, University Medical Center Groningen
Mary K. Wojczynski: Washington University School of Medicine
Xin-Qun Wang: University of Virginia
Raymond Noordam: Section Gerontology and Geriatrics, Leiden University Medical Center
Fernando Pires Hartwig: Federal University of Pelotas
Victoria E. Jackson: University of Leicester
Tianyuan Wang: US Department of Health and Human Services
Ma’en Obeidat: The University of British Columbia Center for Heart Lung Innovation, St Paul’s Hospital
Brian D. Hobbs: Brigham and Women’s Hospital
Tianxiao Huan: Division of Intramural Research, National Heart, Lung, and Blood Institute
Hongsheng Gui: Center for Health Policy and Health Services Research, Henry Ford Health System
Margaret M. Parker: Brigham and Women’s Hospital
Donglei Hu: School of Medicine, University of California San Francisco
Lauren S. Mogil: Department of Biology, Loyola University Chicago
Gleb Kichaev: University of California Los Angeles
Jianping Jin: Westat
Mariaelisa Graff: University of North Carolina
Tamara B. Harris: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Ravi Kalhan: Northwestern University Feinberg School of Medicine
Susan R. Heckbert: Cardiovascular Health Research Unit, University of Washington
Lavinia Paternoster: School of Social and Community Medicine, University of Bristol
Kristin M. Burkart: College of Physicians and Surgeons, Columbia University
Yongmei Liu: Wake Forest School of Medicine
Elizabeth G. Holliday: Hunter Medical Research Institute and Faculty of Health, University of Newcastle
James G. Wilson: University of Mississippi Medical Center
Judith M. Vonk: University of Groningen, University Medical Center Groningen
Jason L. Sanders: Massachusetts General Hospital
R. Graham Barr: College of Physicians and Surgeons, Columbia University
Renée Mutsert: Leiden University Medical Center
Ana Maria Baptista Menezes: Federal University of Pelotas
Hieab H. H. Adams: Erasmus University Medical Center
Maarten Berge: University of Groningen, University Medical Center Groningen
Roby Joehanes: Hebrew SeniorLife, Harvard University
Albert M. Levin: Henry Ford Health System
Jennifer Liberto: School of Medicine, University of California San Francisco
Lenore J. Launer: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Alanna C. Morrison: Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
Colleen M. Sitlani: University of Washington
Juan C. Celedón: Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh
Stephen B. Kritchevsky: Wake Forest School of Medicine
Rodney J. Scott: Hunter Medical Research Institute and Faculty of Health, University of Newcastle
Kaare Christensen: Biostatistics and Biodemography, University of Southern Denmark
Jerome I. Rotter: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
Tobias N. Bonten: Leiden University Medical Center
Fernando César Wehrmeister: Federal University of Pelotas
Yohan Bossé: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University
Shujie Xiao: Center for Health Policy and Health Services Research, Henry Ford Health System
Sam Oh: School of Medicine, University of California San Francisco
Nora Franceschini: University of North Carolina
Jennifer A. Brody: University of Washington
Robert C. Kaplan: Albert Einstein College of Medicine
Kurt Lohman: Wake Forest School of Medicine
Mark McEvoy: Hunter Medical Research Institute and Faculty of Health, University of Newcastle
Michael A. Province: Washington University School of Medicine
Frits R. Rosendaal: Leiden University Medical Center
Kent D. Taylor: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center
David C. Nickle: Merck Research Laboratories, GpGx, Merck & Co., Inc.
L. Keoki Williams: Center for Health Policy and Health Services Research, Henry Ford Health System
Esteban G. Burchard: School of Medicine, University of California San Francisco
Heather E. Wheeler: Department of Biology, Loyola University Chicago
Don D. Sin: The University of British Columbia Center for Heart Lung Innovation, St Paul’s Hospital
Vilmundur Gudnason: Icelandic Heart Association
Kari E. North: University of North Carolina
Myriam Fornage: University of Texas Health Science Center at Houston
Bruce M. Psaty: University of Washington
Richard H. Myers: Boston University School of Medicine
George O’Connor: National Heart, Lung, and Blood Institute’s Framingham Heart Study
Torben Hansen: Metabolic Genetics Section, Faculty of Health and Medical Sciences, University of Copenhagen
Cathy C. Laurie: University of Washington
Patricia A. Cassano: Cornell University
Joohon Sung: School of Public Health, Seoul National University
Woo Jin Kim: Kangwon National University
John R. Attia: Hunter Medical Research Institute and Faculty of Health, University of Newcastle
Leslie Lange: University of Colorado Denver
H. Marike Boezen: University of Groningen, University Medical Center Groningen
Bharat Thyagarajan: University of Minnesota
Stephen S. Rich: University of Virginia
Dennis O. Mook-Kanamori: Leiden University Medical Center
Bernardo Lessa Horta: Federal University of Pelotas
André G. Uitterlinden: Erasmus University Medical Center
Hae Kyung Im: The University of Chicago
Michael H. Cho: Brigham and Women’s Hospital
Guy G. Brusselle: Ghent University Hospital
Sina A. Gharib: Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, University of Washington
Josée Dupuis: Boston University School of Public Health
Ani Manichaikul: University of Virginia
Stephanie J. London: US Department of Health and Human Services

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05369-0

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