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Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Original publication

DOI

10.1038/ng.501

Type

Journal article

Journal

Nat Genet

Publication Date

01/2010

Volume

42

Pages

36 - 44

Keywords

Female, Forced Expiratory Volume, Gene Expression Profiling, Genome, Human, Genome-Wide Association Study, Glutathione Transferase, Humans, Lung, Male, Meta-Analysis as Topic, Microfilament Proteins, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, RNA, Messenger, Receptor for Advanced Glycation End Products, Receptors, Immunologic, Receptors, Serotonin, 5-HT4, Respiratory Function Tests, Spirometry, Tensins, Thrombospondins, Vital Capacity