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dc.contributor.authorWalter, Robert E.
dc.contributor.authorNagle, Michael W.
dc.contributor.authorBrandler, Brian J.
dc.contributor.authorBorecki, Ingrid B.
dc.contributor.authorO'Connor, George T.
dc.contributor.authorMcCarthy, Mark I.
dc.contributor.authorWilk, Jemma B
dc.contributor.authorChen, Ting-Hsu
dc.contributor.authorGottlieb, Daniel J
dc.contributor.authorMyers, Richard Hepworth
dc.contributor.authorSilverman, Edwin Kepner
dc.contributor.authorWeiss, Scott Tillman
dc.date.accessioned2011-04-23T16:57:41Z
dc.date.issued2009
dc.identifier.citationWilk, Jemma B., Ting-hsu Chen, Daniel J. Gottlieb, Robert E. Walter, Michael W. Nagle, Brian J. Brandler, Richard H. Myers, et al. 2009. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genetics 5(3): e1000429.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4874803
dc.description.abstractThe ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09). One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04). The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1000429en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652834/pdf/en_US
dash.licenseLAA
dc.subjectgenetics and genomicsen_US
dc.subjectcomplex traitsen_US
dc.subjectgenetics of diseaseen_US
dc.subjectCOPD and allied disordersen_US
dc.subjectrespiratory medicineen_US
dc.titleA Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Studyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorSilverman, Edwin Kepner
dc.date.available2011-04-23T16:57:41Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Molecular+Integrative Physiological Sci Progen_US
dc.identifier.doi10.1371/journal.pgen.1000429*
dash.authorsorderedfalse
dash.contributor.affiliatedGottlieb, Daniel
dash.contributor.affiliatedMyers, Richard Hepworth
dash.contributor.affiliatedChen, Ting-Hsu
dash.contributor.affiliatedWilk, Jemma
dash.contributor.affiliatedWeiss, Scott
dash.contributor.affiliatedSilverman, Edwin


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