Genome-wide association analysis and replication of coronary artery disease in South Korea suggests a causal variant common to diverse populations.
BACKGROUND
Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations.


METHODS
The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population.


RESULTS
The association previously observed on chromosome 9p21 was independently replicated (p=3.08e-07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population.


CONCLUSIONS
A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors.
DNA Link, Seoul, Republic of Korea.
Eun Young
EY
Cho
Clinical Nutrigenetics/Nutrigenomics Lab, Department of Food & Nutrition, College of Human Ecology, Yonsei University Research Institute of Science for Ageing, Yonsei University, Seoul, Republic of Korea.
Yangsoo
Y
Jang
DNA Link, Seoul, Republic of Korea.
Eun Soon
ES
Shin
DNA Link, Seoul, Republic of Korea.
Hye Yoon
HY
Jang
DNA Link, Seoul, Republic of Korea.
Yeon-Kyeong
YK
Yoo
DNA Link, Seoul, Republic of Korea.
Sook
S
Kim
DNA Link, Seoul, Republic of Korea.
Ji Hyun
JH
Jang
DNA Link, Seoul, Republic of Korea.
Ji Yeon
JY
Lee
DNA Link, Seoul, Republic of Korea.
Min Hye
MH
Yun
DNA Link, Seoul, Republic of Korea.
Min Young
MY
Park
Clinical Nutrigenetics/Nutrigenomics Lab, Department of Food & Nutrition, College of Human Ecology, Yonsei University Research Institute of Science for Ageing, Yonsei University, Seoul, Republic of Korea.
Jey Sook
JS
Chae
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, Republic of Korea.
Jin Woo
JW
Lim
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, Republic of Korea.
Dong Jik
DJ
Shin
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, Republic of Korea.
Sungha
S
Park
Clinical Nutrigenetics/Nutrigenomics Lab, Department of Food & Nutrition, College of Human Ecology, Yonsei University Research Institute of Science for Ageing, Yonsei University, Seoul, Republic of Korea.
Jong Ho
JH
Lee
National Genome Research Institute, Korean National Institute of Health, Seoul, Korea.
Bok Ghee
BG
Han
National Genome Research Institute, Korean National Institute of Health, Seoul, Korea.
Kim Hyung
KH
Rae
GlaxoSmithKline, Philadelphia, Pennsylvania, USA.
Lon R
LR
Cardon
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
Andrew P
AP
Morris
DNA Link, Seoul, Republic of Korea.
Jong Eun
JE
Lee
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
Geraldine M
GM
Clarke
Asian and Caucasian populations; Coronary artery disease; common causal mutation; genetics; genome-wide association study; myocardial infarction; population studies