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Meta-Analysis
. 2018 Jul 30;9(1):2976.
doi: 10.1038/s41467-018-05369-0.

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

Annah B Wyss  1 Tamar Sofer  2   3 Mi Kyeong Lee  1 Natalie Terzikhan  4   5 Jennifer N Nguyen  6 Lies Lahousse  5   7 Jeanne C Latourelle  8 Albert Vernon Smith  9   10   11 Traci M Bartz  12   13 Mary F Feitosa  14 Wei Gao  15 Tarunveer S Ahluwalia  16   17 Wenbo Tang  18 Christopher Oldmeadow  19 Qing Duan  20 Kim de Jong  21 Mary K Wojczynski  14 Xin-Qun Wang  22 Raymond Noordam  23 Fernando Pires Hartwig  24   25 Victoria E Jackson  26 Tianyuan Wang  27 Ma'en Obeidat  28 Brian D Hobbs  29   30 Tianxiao Huan  31 Hongsheng Gui  32 Margaret M Parker  29 Donglei Hu  33 Lauren S Mogil  34 Gleb Kichaev  35 Jianping Jin  36 Mariaelisa Graff  37 Tamara B Harris  38 Ravi Kalhan  39 Susan R Heckbert  40 Lavinia Paternoster  25 Kristin M Burkart  41 Yongmei Liu  42 Elizabeth G Holliday  19 James G Wilson  43 Judith M Vonk  21 Jason L Sanders  44 R Graham Barr  45   46 Renée de Mutsert  47 Ana Maria Baptista Menezes  24 Hieab H H Adams  5   48 Maarten van den Berge  49 Roby Joehanes  50 Albert M Levin  51 Jennifer Liberto  33 Lenore J Launer  38 Alanna C Morrison  52 Colleen M Sitlani  12 Juan C Celedón  53 Stephen B Kritchevsky  54 Rodney J Scott  19   55 Kaare Christensen  56 Jerome I Rotter  57 Tobias N Bonten  58   59 Fernando César Wehrmeister  24 Yohan Bossé  60 Shujie Xiao  32 Sam Oh  33 Nora Franceschini  37 Jennifer A Brody  12 Robert C Kaplan  61 Kurt Lohman  42 Mark McEvoy  19 Michael A Province  14 Frits R Rosendaal  47 Kent D Taylor  57 David C Nickle  62 L Keoki Williams  32   63 Esteban G Burchard  33   64 Heather E Wheeler  34 Don D Sin  28   65 Vilmundur Gudnason  9   10 Kari E North  37 Myriam Fornage  66 Bruce M Psaty  12   40   67   68 Richard H Myers  8 George O'Connor  69   70 Torben Hansen  16 Cathy C Laurie  13 Patricia A Cassano  18   71 Joohon Sung  72 Woo Jin Kim  73 John R Attia  19 Leslie Lange  74 H Marike Boezen  21 Bharat Thyagarajan  75 Stephen S Rich  6 Dennis O Mook-Kanamori  47   58 Bernardo Lessa Horta  24 André G Uitterlinden  76 Hae Kyung Im  77 Michael H Cho  29   30 Guy G Brusselle  4   5   78 Sina A Gharib  79 Josée Dupuis  15   69 Ani Manichaikul  6 Stephanie J London  80
Affiliations
Meta-Analysis

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

Annah B Wyss et al. Nat Commun. .

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.

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Conflict of interest statement

J.C.L. is currently an employee of GNS Healthcare. W.T. is currently an employee of Boehringer Ingelheim Pharmaceuticals. A.M.B.M. has received grant support from GlaxoSmithKline and from AstraZeneca in the last 5 years, but not for the present study. J.C.C. received research materials from Pharmavite (vitamin D and placebo capsules), GSK (Flovent), and Merck (Asmanex) to provide medications free of cost to participants in NIH-funded studies. D.C.N. is an employee of Merck Research Laboratories. D.D.S. has received research funding from Boehringer Ingelheim, Merck, and AstraZeneca outside the scope of this work. B.M.P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. M.H.C. has received grant support from GlaxoSmithKline. The authors declare no other competing interests.

Figures

Fig. 1
Fig. 1
Manhattan plots of genome-wide association results for pulmonary function in the following CHARGE meta-analyses: a FEV1 European ancestry; b FVC European ancestry; c FEV1 /FVC European ancestry; d FEV multiethnic; e FVC multiethnic; f FEV1 /FVC multiethnic. Novel loci indicated by magenta. Significance level (5x10‒8) indicated by dashed line

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