Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study

J Hum Genet. 2018 Mar;63(3):327-337. doi: 10.1038/s10038-017-0384-9. Epub 2018 Jan 10.


Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p < 5.0 × 10-8) for the NOX4 locus (lead variant rs2289125, β = -0.15, p = 5.3 × 1011). While the NOX4 locus was previously reported as associated with Hcy in European-American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.

MeSH terms

  • Adult
  • Alleles
  • Atherosclerosis / blood*
  • Atherosclerosis / epidemiology
  • Atherosclerosis / genetics*
  • Black or African American / genetics*
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Genotype
  • Homocysteine / blood*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mississippi / epidemiology
  • Polymorphism, Single Nucleotide
  • Population Surveillance
  • Quantitative Trait Loci
  • Quantitative Trait, Heritable
  • Young Adult


  • Homocysteine