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

TitleMultiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.
Publication TypeJournal Article
Year of Publication2018
AuthorsWyss AB, Sofer T, Lee MKyeong, et al.
Secondary AuthorsLondon SJ
JournalNat Commun
Volume9
Issue1
Pagination2976
Date Published2018 07 30
ISSN2041-1723
KeywordsAfrican Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Female, Forced Expiratory Volume, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Hispanic Americans, Humans, Linkage Disequilibrium, Lung, Lung Diseases, Male, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Quantitative Trait Loci, Regression Analysis, Sample Size, Smoking, Vital Capacity
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.

DOI10.1038/s41467-018-05369-0
Alternate JournalNat Commun
PubMed ID30061609
PubMed Central IDPMC6065313
Grant ListR01 HL105756 / HL / NHLBI NIH HHS / United States
R15 HG009569 / HG / NHGRI NIH HHS / United States
K08 HL136928 / HL / NHLBI NIH HHS / United States
U01 AG023746 / AG / NIA NIH HHS / United States
R01 HL131565 / HL / NHLBI NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
T32 HL007427 / HL / NHLBI NIH HHS / United States
R01HL105756 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / International
P30 ES009089 / ES / NIEHS NIH HHS / United States