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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.

TitleVariants 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.
Publication TypePublication
Year2019
AuthorsSofer T, Emery L, Jain D, Ellis AM, Laurie CC, Allison MA, Lee J, Kurniansyah N, Kerr KF, González HM, Tarraf W, Criqui MH, Lange LA, Palmas WR, Franceschini N, Wassel CL
JournalSci Rep
Volume9
Issue1
Pagination11410
Date Published2019 08 06
ISSN2045-2322
KeywordsAdolescent, Adult, African Americans, Aged, ankle brachial index, Dystrophin, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, genome-wide association study, Hispanic Americans, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Peripheral Arterial Disease, Polymorphism, Single Nucleotide, Prospective Studies, United States, Young Adult
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) for PAD in MESA Hispanics. Among three suggestive associations (p < 10) in subgroup-specific analyses, DMD on chromosome X, identified in Central Americans, replicated in MESA Hispanics (p = 2.2 × 10). None of the previously reported ABI and PAD associations in whites generalized to Hispanics/Latinos.

DOI10.1038/s41598-019-47928-5
Alternate JournalSci Rep
PubMed ID31388106
PubMed Central IDPMC6684818
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 AG048642 / AG / NIA NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R56 DK104806 / DK / NIDDK NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
RF1 AG054548 / AG / NIA NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL110955 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
MS#: 
0345
Manuscript Lead/Corresponding Author Affiliation: 
Affiliated Investigator - Not at HCHS/SOL site
ECI: 
Manuscript Status: 
Published