Epidemiology and genetic determination of measures of peripheral vascular health in the Long Life Family Study

Peripheral artery disease (PAD) is a major contributor to morbidity in older adults. We aimed to determine genetic and non-genetic determinants of PAD and ankle-brachial index (ABI) in the Long Life Family Study (LLFS). 3006 individuals had ABI assessment, including 1090 probands (mean age 89), 1554 offspring (mean age 60) and 362 spousal controls (mean age 61). Outcomes include minimum of right and left ABIs and PAD (ABI <0.9). Stepwise regression determined independent significant non-genetic correlates of ABI and PAD. Genomewide association and linkage analyses were adjusted for age, sex, study center, significant principal components, and independent predictors. All analyses accounted for familial relatedness. Median ABI was 1.16 and 7.4% had PAD (18.2% probands, 1.0% offspring, 1.9% controls). Correlates of PAD and lower ABI included age, SBP, and creatinine (ABI only); BMI (ABI only), HDL (ABI only) and DBP (PAD only); and antihypertensive use, current smoking, female sex (ABI only), and high school noncompletion (ABI only). Genomewide linkage identified 1 region (15q12-q13) and association identified 3 single nucleotide polymorphisms (rs780213, rs12512857, rs79644420) of interest. In these families, PAD prevalence was low compared to other studies of older adults. We identified four genomic sites that may harbor variants associated with protection from PAD.