Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
Recommended Citation
Wyss AB, Sofer T, Lee MK, Terzikhan N, Nguyen JN, Lahousse L, Latourelle JC, Smith AV, Bartz TM, Feitosa MF, Gao W, Ahluwalia TS, Tang W, Oldmeadow C, Duan Q, de Jong K, Wojczynski MK, Wang X, Noordam R, Hartwig FP, Jackson VE, Wang T, Obeidat M, Hobbs BD, Huan T, Gui H, Parker MM, Hu D, Mogil LS, Kichaev G, Jin J, Graff M, Harris T, Kalhan R, Heckbert S, Paternoster L, Burkart K, Liu Y, Holliday E, Wilson J, Vonk J, Sanders J, Barr R, de Mutsert R, Menezes A, Adams H, van den Berge M, Joehanes R, Levin AM, Liberto J, Launer L, Morrison A, Sitlani C, Celedón J, Kritchevsky S, Scott R, Christensen K, Rotter J, Bonten T, Wehrmeister F, Bossé Y, Xiao S, Oh S, Franceschini N, Brody J, Kaplan R, Lohman K, McEvoy M, Province M, Rosendaal F, Taylor K, Nickle D, Williams KL, Burchard E, Wheeler H, Sin D, Gudnason V, North K, Fornage M, Psaty B, Myers R, O'Connor G, Hansen T, Laurie C, Cassano P, Sung J, Kim W, Attia J, Lange L, Boezen H, Thyagarajan B, Rich S, Mook-Kanamori D, Horta B, Uitterlinden A, Im H, Cho M, Brusselle G, Gharib S, Dupuis J, Manichaikul A, London S. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nat Commun 2018; 9(1):2976-2976.
Document Type
Article
Publication Date
7-30-2018
Publication Title
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.
Medical Subject Headings
African 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
PubMed ID
30061609
Volume
9
Issue
1
First Page
2976
Last Page
2976
