Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV₁/FVC in the COPDGene Study

ABSTRACT

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 FEV₁/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 FEV₁/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 FEV₁/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 FEV₁/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 FEV₁/FVC ratio among African Americans in the COPDGene Study.