A genome-wide association study of a coronary artery disease risk variant.
Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS), genetic risk variants reported to date explain only a small fraction of heritability. To identify novel susceptibility variants for CAD and confirm those previously identified in European population, GWAS and a replication study were performed in the Koreans and Japanese. In the discovery stage, we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean. In the replication, direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs. To maximize the coverage of the genome, imputation was performed based on 1000 Genome JPT+CHB and 5.1 million SNPs were retained. CAD association was replicated for three GWAS-identified loci (1p13.3/SORT1 (rs599839), 9p21.3/CDKN2A/2B (rs4977574), and 11q22.3/ PDGFD (rs974819)) in Koreans. From GWAS and a replication, SNP rs3782889 showed a strong association (combined P=3.95 × 10(-14)), although the association of SNP rs3782889 doesn't remain statistically significant after adjusting for SNP rs11066015 (proxy SNP with BRAP (r(2)=1)). But new possible CAD-associated variant was observed for rs9508025 (FLT1), even though its statistical significance did marginally reach at the genome-wide a significance level (combined P=6.07 × 10(-7)). This study shows that three CAD susceptibility loci, which were previously identified in European can be directly replicated in Koreans and also provides additional evidences implicating suggestive loci as risk variants for CAD in East Asian.
Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Korea. leejy63@nih.go.kr
Ji-Young
JY
Lee
Bok-Soo
BS
Lee
Dong-Jik
DJ
Shin
Kyung
K
Woo Park
Young-Ah
YA
Shin
Kwang
K
Joong Kim
Lyong
L
Heo
Ji
J
Young Lee
Yun
Y
Kyoung Kim
Young
Y
Jin Kim
Chang
C
Bum Hong
Sang-Hak
SH
Lee
Dankyu
D
Yoon
Hyo
H
Jung Ku
Il-Young
IY
Oh
Bong-Jo
BJ
Kim
Juyoung
J
Lee
Seon-Joo
SJ
Park
Jimin
J
Kim
Hye-Kyung
HK
Kawk
Jong-Eun
JE
Lee
Hye-Kyung
HK
Park
Jae-Eun
JE
Lee
Hye-Young
HY
Nam
Hyun-Young
HY
Park
Chol
C
Shin
Mitsuhiro
M
Yokota
Hiroyuki
H
Asano
Masahiro
M
Nakatochi
Tatsuaki
T
Matsubara
Hidetoshi
H
Kitajima
Ken
K
Yamamoto
Hyung-Lae
HL
Kim
Bok-Ghee
BG
Han
Myeong-Chan
MC
Cho
Yangsoo
Y
Jang
Hyo-Soo
HS
Kim
Jeong
J
Euy Park
Jong-Young
JY
Lee
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors