Abstract
Lower extremity peripheral artery disease (PAD) burden differs by race/ethnicity. Although familial aggregation and heritability studies suggest a genetic basis, little is known about the genetic susceptibility to PAD, especially in non-European descent populations. Genome-wide association studies (GWAS) of the ankle brachial index (ABI) and PAD (defined as an ABI < 0.90) have not been conducted in Hispanics/Latinos. We performed a GWAS of PAD and the ABI in 7,589 participants aged >45 years from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We also performed GWAS for ABI stratified by Hispanic/Latino ethnic subgroups: Central American, Mexican, and South American (Mainland group), and Cuban, Dominican, and Puerto Rican (Caribbean group). We detected two genome-wide significant associations for the ABI in COMMD10 in Puerto Ricans, and at SYBU in the Caribbean group. The lead SNP rs4466200 in the COMMD10 gene had a replication p = 0.02 for the ABI in Multi-Ethnic Study of Atherosclerosis (MESA) African Americans, but it did not replicate in African Americans from the Cardiovascular Health Study (CHS). In a regional look-up, a nearby SNP rs12520838 had Bonferroni adjusted p = 0.05 (unadjusted p = 7.5 × 10−5) for PAD in MESA Hispanics. Among three suggestive associations (p < 10−7) in subgroup-specific analyses, DMD on chromosome X, identified in Central Americans, replicated in MESA Hispanics (p = 2.2 × 10−4). None of the previously reported ABI and PAD associations in whites generalized to Hispanics/Latinos.
Highlights
Www.nature.com/scientificreports or via other criteria, is associated with an increased risk for incident cardiovascular disease (CVD) events and mortality[2,3,4,5,6]
ankle brachial index (ABI) distribution varied in ethnic subgroups with the lowest mean among Cuban Americans, and highest mean among Mexican Americans
We examined the genetic architecture underlying ABI and peripheral artery disease (PAD) in the Hispanic/Latino population using a large cohort of ancestrally diverse Hispanics/Latinos living in the US
Summary
Www.nature.com/scientificreports or via other criteria, is associated with an increased risk for incident cardiovascular disease (CVD) events and mortality[2,3,4,5,6]. The burden of PAD is greater in African-Americans and Cuban Americans compared to non-Hispanic whites and other Hispanic groups such as Mexican Americans[8,9] These race/ethnic differences have not been explained by traditional, genetic, or novel risk factors to date[10,11,12]. A variant in TCF7L2 was significantly associated with ABI in a large-scale candidate gene (∼50 K SNPs) analysis of European ancestry (n = 21,000), but this association failed to replicate in independent samples[12]. We sought to identify novel loci associations with ABI and PAD in a large cohort of US Hispanics/ Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) using GWAS, replicate novel associations in independent samples, and to study whether previously identified genetic variants in European ancestry generalize to Hispanics/Latinos. We performed GWAS for ABI in subgroups based on participant background, using genetically estimated ancestry and self-reported ethnicity, while taking into account their genetic and environmental heterogeneity
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