New Results
Multiethnic meta-analysis identifies new 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 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
doi: https://doi.org/10.1101/196048
Annah B. Wyss
1Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
Tamar Sofer
2Department of Biostatistics, University of Washington, Seattle, Washington, USA
Mi Kyeong Lee
1Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
Natalie Terzikhan
3Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
4Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
Jennifer N. Nguyen
5Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA
Lies Lahousse
3Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
4Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
Jeanne C. Latourelle
6Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA
Albert Vernon Smith
7Icelandic Heart Association, Kopavogur, Iceland
8Faculty of Medicine, University of Iceland, Reykjavik, Iceland
9Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
Traci M. Bartz
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA
11Cardiovascular Health Research Unit, Department of Biostatistics, University of Washington, Seattle, Washington, USA
Mary F. Feitosa
12Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA
Wei Gao
13Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
Tarunveer S. Ahluwalia
14The Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Genetics Section, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
15Steno Diabetes Center Copenhagen, Gentofte, Denmark
Wenbo Tang
16Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
Christopher Oldmeadow
17Hunter Medical Research Institute and Faculty of Health, University of Newcastle, NSW, Australia
Qing Duan
18Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA
Kim de Jong
19University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands
Mary K. Wojczynski
12Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA
Xin-Qun Wang
20Division of Biostatistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA
Raymond Noordam
21Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
Fernando Pires Hartwig
22Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
23Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK
Victoria E. Jackson
24Department of Health Sciences, University of Leicester, Leicester, UK
Tianyuan Wang
25Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
Ma’en Obeidat
26The University of British Columbia Center for Heart Lung Innovation, St Paul’s Hospital, Vancouver, British Columbia, Canada
Brian D. Hobbs
27Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
28Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Tianxiao Huan
29National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Gleb Kichaev
30University of California Los Angeles, Los Angeles, California, USA
Jianping Jin
31Westat, Durham, North Carolina, USA
Mariaelisa Graff
32Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
Tamara B. Harris
33Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Ravi Kalhan
34Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Susan R. Heckbert
35Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, USA
Lavinia Paternoster
23Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK
Kristin M. Burkart
36Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA
Yongmei Liu
37Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Elizabeth G. Holliday
17Hunter Medical Research Institute and Faculty of Health, University of Newcastle, NSW, Australia
James G. Wilson
38Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA
Judith M. Vonk
19University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands
Jason Sanders
39Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
R. Graham Barr
40Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA
41Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
Renée de Mutsert
42Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Ana Maria Baptista Menezes
22Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
Hieab H. H. Adams
4Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
43Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands
Maarten van den Berge
44University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands
Roby Joehanes
45Hebrew SeniorLife, Harvard University, Boston, Massachusetts, USA
Lenore J. Launer
33Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Alanna C. Morrison
46Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA
Colleen M. Sitlani
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA
Juan C. Celedón
47Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Stephen B. Kritchevsky
48Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Rodney J. Scott
17Hunter Medical Research Institute and Faculty of Health, University of Newcastle, NSW, Australia
49Division of Molecular Medicine, Pathology North, NSW Health Pathology, Newcastle, NSW, Australia
Kaare Christensen
50Department of Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, Odense, Denmark
Jerome I. Rotter
51Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA
Tobias N. Bonten
52Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands
53Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands
Fernando César Wehrmeister
22Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
Yohan Bossé
54Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec, Canada
Nora Franceschini
32Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
Jennifer A. Brody
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA
Robert C. Kaplan
55Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
Kurt Lohman
37Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Mark McEvoy
17Hunter Medical Research Institute and Faculty of Health, University of Newcastle, NSW, Australia
Michael A. Province
12Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA
Frits R. Rosendaal
42Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Kent D. Taylor
51Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA
David C. Nickle
56Merck Research Laboratories, GpGx, Merck & Co., Inc., Kenilworth, New Jersey, USA
7Icelandic Heart Association, Kopavogur, Iceland
8Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Kari E. North
32Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
Myriam Fornage
57Brown Foundation Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA
Bruce M. Psaty
10Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA
35Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, USA
58Cardiovascular Health Research Unit, Department of Health Services, University of Washington, Seattle, Washington, USA
59Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA
Richard H. Myers
6Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA
George O’Connor
60National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA
61Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
Torben Hansen
14The Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Genetics Section, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Cathy C. Laurie
2Department of Biostatistics, University of Washington, Seattle, Washington, USA
Pat Cassano
16Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
62Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York, USA
Joohon Sung
63Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea
Woo Jin Kim
64Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, South Korea
John R. Attia
17Hunter Medical Research Institute and Faculty of Health, University of Newcastle, NSW, Australia
Leslie Lange
65University of Colorado Denver, Denver, Colorado, USA
H. Marike Boezen
19University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands
Bharat Thyagarajan
66Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
Stephen S. Rich
5Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA
Dennis O. Mook-Kanamori
42Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
52Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands
Bernardo Lessa Horta
22Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
André G Uitterlinden
67Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Don D. Sin
26The University of British Columbia Center for Heart Lung Innovation, St Paul’s Hospital, Vancouver, British Columbia, Canada
68Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Hae Kyung Im
69Section of Genetic Medicine, The University of Chicago, Chicago, Illinois, USA
Michael H. Cho
27Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
28Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Guy G. Brusselle
3Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
4Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
70Department of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Sina A. Gharib
71Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, Washington, USA
Josée Dupuis
13Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
60National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA
Ani Manichaikul
5Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA
Stephanie J. London
1Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
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=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.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
Posted October 05, 2017.
Multiethnic meta-analysis identifies new 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 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
bioRxiv 196048; doi: https://doi.org/10.1101/196048
Multiethnic meta-analysis identifies new 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 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
bioRxiv 196048; doi: https://doi.org/10.1101/196048
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