Variants Associated with the Ankle Brachial Index Differ by Hispanic/Latino Ethnic Group: a genome-wide association study in the Hispanic Community Health Study/Study of Latinos

Sci Rep. 2019 Aug 6;9(1):11410. doi: 10.1038/s41598-019-47928-5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • African Americans / genetics
  • Aged
  • Ankle Brachial Index*
  • Dystrophin / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Hispanic Americans / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / epidemiology
  • Peripheral Arterial Disease / ethnology
  • Peripheral Arterial Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • United States
  • Young Adult

Substances

  • COMMD10 protein, human
  • DMD protein, human
  • Dystrophin
  • Intracellular Signaling Peptides and Proteins