Dataset Information

Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.

ABSTRACT: RATIONALE:Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied. OBJECTIVES:To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP. METHODS:By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD. MEASUREMENTS AND MAIN RESULTS:Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (? = -72.21 ml, P = 3.90 × 10(-4)) and FEV1/FVC (? = -1.53%, P = 6.35 × 10(-6)), and with COPD (odds ratio = 1.63, P = 1.46 × 10(-5)). CONCLUSIONS:Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.

SUBMITTER: Soler Artigas M

PROVIDER: S-EPMC3398416 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.

Soler Artigas María M Wain Louise V LV Repapi Emmanouela E Obeidat Ma'en M Sayers Ian I Burton Paul R PR Johnson Toby T Zhao Jing Hua JH Albrecht Eva E Dominiczak Anna F AF Kerr Shona M SM Smith Blair H BH Cadby Gemma G Hui Jennie J Palmer Lyle J LJ Hingorani Aroon D AD Wannamethee S Goya SG Whincup Peter H PH Ebrahim Shah S Smith George Davey GD Barroso Inês I Loos Ruth J F RJ Wareham Nicholas J NJ Cooper Cyrus C Dennison Elaine E Shaheen Seif O SO Liu Jason Z JZ Marchini Jonathan J Dahgam Santosh S Naluai Asa Torinsson AT Olin Anna-Carin AC Karrasch Stefan S Heinrich Joachim J Schulz Holger H McKeever Tricia M TM Pavord Ian D ID Heliövaara Markku M Ripatti Samuli S Surakka Ida I Blakey John D JD Kähönen Mika M Britton John R JR Nyberg Fredrik F Holloway John W JW Lawlor Debbie A DA Morris Richard W RW James Alan L AL Jackson Cathy M CM Hall Ian P IP Tobin Martin D MD

American journal of respiratory and critical care medicine 20111001 7

<h4>Rationale</h4>Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied.<h4>Objectives</h4>To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and varia ...[more]

PMID: 21965014

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Project description:COPD is a major cause of disability, but little is known about how disability develops in this condition.The authors analysed data from the Function, Living, Outcomes and Work (FLOW) Study which enrolled 1202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1051 subjects at 2-year follow-up. The authors tested the specific hypothesis that the development of specific non-respiratory impairments (abnormal body composition and muscle strength) and functional limitations (decreased lower extremity function, poor balance, mobility-related dyspnoea, reduced exercise performance and decreased cognitive function) will determine the risk of disability in COPD, after controlling for respiratory impairment (FEV(1) and oxygen saturation). The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities. The primary disability outcome measure was defined as an increase in the proportion of activities that cannot be performed of 3.3% or greater from baseline to 2-year follow-up (the estimated minimal important difference). Multivariable logistic regression was used for analysis.Respiratory impairment measures were related to an increased prospective risk of disability (multivariate OR 1.75; 95% CI 1.26 to 2.44 for 1 litre decrement of FEV(1) and OR 1.57 per 5% decrement in oxygen saturation; 95% CI 1.13 to 2.18). Non-respiratory impairment (body composition and lower extremity muscle strength) and functional limitations (lower extremity function, exercise performance, and mobility-related dyspnoea) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment (p<0.05 in all cases). Non-respiratory impairment and functional limitations were predictive of prospective disability, above-and-beyond sociodemographic characteristics, smoking status and respiratory impairment (area under the receiver operating characteristic curve increased from 0.65 to 0.75; p<0.001).Development of non-respiratory impairment and functional limitations, which reflect the systemic nature of COPD, appear to be critical determinants of disablement. Prevention and treatment of disability require a comprehensive approach to the COPD patient.

Dataset Information

Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.

Publications

Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.

Similar Datasets

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