Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV1/FVC in the COPDGene Study. Issue 7 (11th August 2014)

• Record Type: Journal Article
• Authors: Parker, Margaret M.; Foreman, Marilyn G.; Abel, Haley J.; Mathias, Rasika A.; Hetmanski, Jacqueline B.; Crapo, James D.; Silverman, Edwin K.; Beaty, Terri H.; the COPDGene Investigators
• Is Part Of: Genetic epidemiology. Volume 38:Issue 7(2014)
• Page Start: 652
• Page End: 659
• Publication Date: 2014-08-11
• Subjects: Genetic epidemiology -- Periodicals; Heredity -- Periodicals; Medical geography -- Periodicals; 614
• DOI: 10.1002/gepi.21847
• Languages: English
• ISSNs: 0741-0395

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>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<sub>1</sub>/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<sub>1</sub>/FVC (<italic>P</italic> = 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<sub>1</sub>/FVC (<italic>P</italic> = 2.1 × 10<sup>−6</sup>) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in <italic>FAM19A2</italic> (rs348644) as associated with FEV<sub>1</sub>/FVC (<italic>P</italic> = 1.76 × 10<sup>−6</sup>). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV<sub>1</sub>/FVC ratio among African Americans in the COPDGene Study.</p> </abstract>