TY - JOUR
T1 - 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
AU - Raffield, L. M.
AU - Ellis, Jaclyn
AU - Olson, Nels C.
AU - Duan, Qing
AU - Li, Jin
AU - Durda, Peter
AU - Pankratz, Nathan
AU - Keating, Brendan J.
AU - Wassel, Christina L.
AU - Cushman, Mary
AU - Wilson, James G.
AU - Gross, Myron D.
AU - Tracy, Russell P.
AU - Rich, Stephen S.
AU - Reiner, Alex P.
AU - Li, Yun
AU - Willis, Monte S.
AU - Lange, Ethan M.
AU - Lange, Leslie A.
N1 - Publisher Copyright:
© 2017 The Japan Society of Human Genetics.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s10038-017-0384-9
DO - 10.1038/s10038-017-0384-9
M3 - Article
C2 - 29321517
AN - SCOPUS:85040371045
SN - 1434-5161
VL - 63
SP - 327
EP - 337
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 3
ER -
