Heterogeneous effects of association between blood pressure loci and coronary artery disease in east Asian individuals.
BACKGROUND
A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations.


RESULTS
Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD case-control samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations at FIGN,FGF5 and NPR3, and 2 previously reported ones at ATP2B1 and CNNM2. The strongest CAD association was detected at ATP2B1rs2681472 (P=1.7×10(-8)), in the direction inverted to what is generally recognized for BP in the epidemiological studies.CNNM2rs12413409 showed significant association with CAD (P=8.7×10(-7)) and BMI (P=3.5×10(-8), when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011).


CONCLUSIONS
A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference.
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine.
Fumihiko
F
Takeuchi
Masato
M
Isono
Ken
K
Yamamoto
Mitsuhiro
M
Yokota
Koichi
K
Akiyama
Tomohiro
T
Katsuya
Hyo-Soo
HS
Kim
Jeong Euy
JE
Park
Yangsoo
Y
Jang
Ji-Young
JY
Lee
Jong-Young
JY
Lee
Norihiro
N
Kato
D000328:Adult; D000368:Aged; D044466:Asian People; D001794:Blood Pressure / Q000235:genetics*; D027682:Cation Transport Proteins; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D016213:Cyclins / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C506952:ATP2B1 protein, human; C558175:CNNM2 protein, human; D027682:Cation Transport Proteins; D016213:Cyclins; D053499:Plasma Membrane Calcium-Transporting ATPases