A genome-wide association study of a coronary artery disease risk variant View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-03

AUTHORS

Ji-Young Lee, Bok-Soo Lee, Dong-Jik Shin, Kyung Woo Park, Young-Ah Shin, Kwang Joong Kim, Lyong Heo, Ji Young Lee, Yun Kyoung Kim, Young Jin Kim, Chang Bum Hong, Sang-Hak Lee, Dankyu Yoon, Hyo Jung Ku, Il-Young Oh, Bong-Jo Kim, Juyoung Lee, Seon-Joo Park, Jimin Kim, Hye-kyung Kawk, Jong-Eun Lee, Hye-kyung Park, Jae-Eun Lee, Hye-young Nam, Hyun-young Park, Chol Shin, Mitsuhiro Yokota, Hiroyuki Asano, Masahiro Nakatochi, Tatsuaki Matsubara, Hidetoshi Kitajima, Ken Yamamoto, Hyung-Lae Kim, Bok-Ghee Han, Myeong-Chan Cho, Yangsoo Jang, Hyo-Soo Kim, Jeong Euy Park, Jong-Young Lee

ABSTRACT

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. More... »

PAGES

120

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/jhg.2012.124

    DOI

    http://dx.doi.org/10.1038/jhg.2012.124

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1000393061

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23364394


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