Genome-wide association study identifies five loci associated with lung function.

Nat Genet 2010 Jan 13;42(1):36-44. Epub 2009 Dec 13.

Departments of Health Sciences and Genetics, Adrian Building, University of Leicester, Leicester, UK.

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.

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January 2010
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References

(Supplied by CrossRef)

PK Myint et al.
Eur. Respir. J. 2005

HJ Schünemann et al.
Chest 2000

DP Strachan et al.
J. Epidemiol. Community Health 1992

RP Young et al.
Eur. Respir. J. 2007

HB Hubert et al.
Am. Rev. Respir. Dis. 1982

GE McClearn et al.
J. Gerontol. 1994

FI Lewitter et al.
Am. J. Epidemiol. 1984

LJ Palmer et al.
Eur. Respir. J. 2001

RJ Loos et al.
Nat. Genet. 2008

SG Pillai et al.
PLoS Genet. 2009

JB Wilk et al.
PLoS Genet. 2009

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