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

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

doi:10.1038/jhg.2012.124

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

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 KawkJong 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

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

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 (r²=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.

Original language	English
Pages (from-to)	120-126
Number of pages	7
Journal	Journal of Human Genetics
Volume	58
Issue number	3
DOIs	https://doi.org/10.1038/jhg.2012.124
State	Published - 1 Mar 2013

Keywords

coronary artery disease
genome-wide association study
polymorphism

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10.1038/jhg.2012.124

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Lee, J. Y., Lee, B. S., Shin, D. J., Woo Park, K., Shin, Y. A., Joong Kim, K., Heo, L., Lee, J. Y., Kim, Y. K., Jin Kim, Y., Hong, C. B., Lee, S. H., Yoon, D., Jung Ku, H., Oh, I. Y., Kim, B. J., Lee, J., Park, S. J., Kim, J., ... Lee, J. Y. (2013). A genome-wide association study of a coronary artery disease risk variant. Journal of Human Genetics, 58(3), 120-126. https://doi.org/10.1038/jhg.2012.124

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title = "A genome-wide association study of a coronary artery disease risk variant",

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 (r2=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.",

keywords = "coronary artery disease, genome-wide association study, polymorphism",

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

year = "2013",

month = mar,

day = "1",

doi = "10.1038/jhg.2012.124",

language = "English",

volume = "58",

pages = "120--126",

journal = "Journal of Human Genetics",

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Lee, JY, Lee, BS, Shin, DJ, Woo Park, K, Shin, YA, Joong Kim, K, Heo, L, Lee, JY, Kim, YK, Jin Kim, Y, Hong, CB, Lee, SH, Yoon, D, Jung Ku, H, Oh, IY, Kim, BJ, Lee, J, Park, SJ, Kim, J, Kawk, HK, Lee, JE, Park, HK, Lee, JE, Nam, HY, Park, HY, Shin, C, Yokota, M, Asano, H, Nakatochi, M, Matsubara, T, Kitajima, H, Yamamoto, K, Kim, HL, Han, BG, Cho, MC, Jang, Y, Kim, HS, Euy Park, J & Lee, JY 2013, 'A genome-wide association study of a coronary artery disease risk variant', Journal of Human Genetics, vol. 58, no. 3, pp. 120-126. https://doi.org/10.1038/jhg.2012.124

TY - JOUR

T1 - A genome-wide association study of a coronary artery disease risk variant

AU - Lee, Ji Young

AU - Lee, Bok Soo

AU - Shin, Dong Jik

AU - Woo Park, Kyung

AU - Shin, Young Ah

AU - Joong Kim, Kwang

AU - Heo, Lyong

AU - Lee, Ji Young

AU - Kim, Yun Kyoung

AU - Jin Kim, Young

AU - Hong, Chang Bum

AU - Lee, Sang Hak

AU - Yoon, Dankyu

AU - Jung Ku, Hyo

AU - Oh, Il Young

AU - Kim, Bong Jo

AU - Lee, Juyoung

AU - Park, Seon Joo

AU - Kim, Jimin

AU - Kawk, Hye Kyung

AU - Lee, Jong Eun

AU - Park, Hye Kyung

AU - Lee, Jae Eun

AU - Nam, Hye Young

AU - Park, Hyun Young

AU - Shin, Chol

AU - Yokota, Mitsuhiro

AU - Asano, Hiroyuki

AU - Nakatochi, Masahiro

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AU - Kitajima, Hidetoshi

AU - Yamamoto, Ken

AU - Kim, Hyung Lae

AU - Han, Bok Ghee

AU - Cho, Myeong Chan

AU - Jang, Yangsoo

AU - Kim, Hyo Soo

AU - Euy Park, Jeong

AU - Lee, Jong Young

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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 (r2=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.

AB - 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 (r2=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.

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KW - polymorphism

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

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Keywords

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