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Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV 1 /FVC in the COPDGene Study
Author(s) -
Parker Margaret M.,
Foreman Marilyn G.,
Abel Haley J.,
Mathias Rasika A.,
Hetmanski Jacqueline B.,
Crapo James D.,
Silverman Edwin K.,
Beaty Terri H.
Publication year - 2014
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21847
Subject(s) - vital capacity , spirometry , body mass index , quantitative trait locus , genetic admixture , demography , allele , genetics , medicine , biology , population , gene , environmental health , lung function , lung , asthma , diffusing capacity , sociology
African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3,300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV 1 /FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV 1 /FVC ( P = 0.035). Genome‐wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack‐years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV 1 /FVC ( P = 2.1 × 10 −6 ) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV 1 /FVC ( P = 1.76 × 10 −6 ). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV 1 /FVC ratio among African Americans in the COPDGene Study.