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BMC Medical Genetics

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Open Access 01-09-2007 | Research

Framingham Heart Study genome-wide association: results for pulmonary function measures

Authors: Jemma B Wilk, Robert E Walter, Jason M Laramie, Daniel J Gottlieb, George T O'Connor

Published in: BMC Medical Genetics | Special Issue 1/2007

Abstract

Background

Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable. We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.

Methods

Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), forced expiratory flow from the 25^th to 75^th percentile (FEF_25–75), the FEV₁/FVC ratio, and the FEF_25–75/FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.

Results

Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency ≥ 10%, genotype call rate ≥ 80%, and Hardy-Weinberg equilibrium p-value ≥ 0.001. A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF_25–75. A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV₁ and FVC measurements from two examinations. SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.

Conclusion

GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.

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Title: Framingham Heart Study genome-wide association: results for pulmonary function measures
Authors: Jemma B Wilk
Robert E Walter
Jason M Laramie
Daniel J Gottlieb
George T O'Connor
Publication date: 01-09-2007
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue Special Issue 1/2007
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-8-S1-S8

At a glance: The STEP trials

Springer Medicine

Framingham Heart Study genome-wide association: results for pulmonary function measures

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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