A genome-wide linkage scan for ankle-brachial index in African American and non-Hispanic white subjects participating in the GENOA study

Abstract

Little is known about the genetics of peripheral arterial disease (PAD). We performed linkage analyses to identify genomic regions that influence ankle-brachial index (ABI), a measure of PAD, in 1310 African Americans (AA) (mean age 62+/-9 years) and 796 non-Hispanic whites (NHW) (mean age 58+/-9 years) belonging to hypertensive sibships. ABI was determined at two sites in each lower extremity and the lower of the two average ABIs was used in the analyses after adjustment for age, age(2), sex, weight, total cholesterol, HDL cholesterol, and ever-smoking. Genotypes were measured at microsatellite marker loci spaced approximately 10cM apart across the 22 autosomes. Heritability was assessed by SOLAR and linkage analyses performed using a variance components approach. Modest heritability (h(2)) was noted for the fully adjusted ABI in each ethnic group (h(2)=0.195, P=0.002 in AA; h(2)=0.212, P=0.006 in NHW). Univariate linkage analyses demonstrated tentative evidence of linkage (multipoint LOD=1.3-2.0) for ABI on chromosomes 1p, 6q, 7q, 10p, and 16p in AA and on chromosome 3p and 3q in NHW. In conclusion, ABI is a modestly heritable trait in AA and NHW hypertensive sibships. Quantitative trait linkage analyses identified several chromosomal regions that may harbor genes influencing ABI.