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

被引：119

作者：

Lee, Ji-Young ^{[1
]}

Lee, Bok-Soo ^{[2
]}

Shin, Dong-Jik ^{[3
]}

Park, Kyung Woo ^{[4
]}

Shin, Young-Ah ^{[1
]}

Kim, Kwang Joong ^{[1
]}

Heo, Lyong ^{[1
]}

Lee, Ji Young ^{[1
]}

Kim, Yun Kyoung ^{[1
]}

Kim, Young Jin ^{[1
]}

Hong, Chang Bum ^{[1
]}

Lee, Sang-Hak ^{[3
]}

Yoon, Dankyu ^{[5
]}

Ku, Hyo Jung ^{[2
]}

Oh, Il-Young ^{[4
]}

Kim, Bong-Jo ^{[1
]}

Lee, Juyoung ^{[1
]}

Park, Seon-Joo ^{[1
]}

Kim, Jimin ^{[1
]}

Kawk, Hye-kyung ^{[1
]}

Lee, Jong-Eun ^{[6
]}

Park, Hye-kyung ^{[1
]}

Lee, Jae-Eun ^{[1
]}

Nam, Hye-young ^{[1
]}

Park, Hyun-young ^{[7
]}

Shin, Chol ^{[8
]}

Yokota, Mitsuhiro ^{[9
]}

Asano, Hiroyuki ^{[10
]}

Nakatochi, Masahiro ^{[11
]}

Matsubara, Tatsuaki ^{[12
]}

Kitajima, Hidetoshi ^{[13
]}

Yamamoto, Ken ^{[13
]}

Kim, Hyung-Lae ^{[14
]}

Han, Bok-Ghee ^{[1
]}

Cho, Myeong-Chan ^{[15
]}

Jang, Yangsoo ^{[3
]}

Kim, Hyo-Soo ^{[4
]}

Park, Jeong Euy ^{[2
]}

Lee, Jong-Young ^{[1
]}

机构：

[1] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do 363951, South Korea

[2] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Cardiol, Seoul, South Korea

[3] Yonsei Univ, Coll Med, Dept Internal Med, Cardiol Div,Cardiovasc Genome Ctr, Seoul, South Korea

[4] Seoul Natl Univ Hosp, Ctr Cardiovasc, Dept Internal Med, Seoul 110744, South Korea

[5] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea

[6] DNA Link, Seoul, South Korea

[7] Natl Inst Hlth, Ctr Biomed Sci, Div Cardiovasc Dis, Chungcheongbuk Do 363951, South Korea

[8] Korea Univ, Ansan Hosp, Div Pulm & Crit Care Med, Ansan, South Korea

[9] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan

[10] Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi 4648601, Japan

[11] Nagoya Univ, Sch Engn, Dept Biotechnol, Nagoya, Aichi, Japan

[12] Aichi Gakuin Univ, Sch Dent, Dept Internal Med, Nagoya, Aichi 464, Japan

[13] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Fukuoka 812, Japan

[14] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul, South Korea

[15] Natl Inst Hlth, Chungcheongbuk Do 363951, South Korea

来源：

JOURNAL OF HUMAN GENETICS | 2013年 / 58卷 / 03期

关键词：

coronary artery disease; genome-wide association study; polymorphism; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; COMMON VARIANTS; BLOOD-PRESSURE; HEART-DISEASE; METAANALYSIS; GENETICS;

D O I：

10.1038/jhg.2012.124

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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 x 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. Journal of Human Genetics (2013) 58, 120-126; doi:10.1038/jhg.2012.124; published online 31 January 2013

引用

页码：120 / 126

页数：7

共 29 条

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← 1 2 3 →

共 29 条

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Asano, H. ;

Izawa, H. ;

Nagata, K. ;

Nakatochi, M. ;

Kobayashi, M. ;

Hirashiki, A. ;

Shintani, S. ;

Nishizawa, T. ;

Tanimura, D. ;

Naruse, K. ;

Matsubara, T. ;

Murohara, T. ;

Yokota, M. .

DIABETOLOGIA, 2010, 53 (02) :234-246

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Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

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Cho, Yoon Shin ;

Go, Min Jin ;

Kim, Young Jin ;

Heo, Jee Yeon ;

Oh, Ji Hee ;

Ban, Hyo-Jeong ;

Yoon, Dankyu ;

Lee, Mi Hee ;

Kim, Dong-Joon ;

Park, Miey ;

Cha, Seung-Hun ;

Kim, Jun-Woo ;

Han, Bok-Ghee ;

Min, Haesook ;

Ahn, Younjhin ;

Park, Man Suk ;

Han, Hye Ree ;

Jang, Hye-Yoon ;

Cho, Eun Young ;

Lee, Jong-Eun ;

Cho, Nam H. ;

Shin, Chol ;

Park, Taesung ;

Park, Ji Wan ;

Lee, Jong-Keuk ;

Cardon, Lon ;

Clarke, Geraldine ;

McCarthy, Mark I. ;

Lee, Jong-Young ;

Lee, Jong-Koo ;

Oh, Bermseok ;

Kim, Hyung-Lae .

NATURE GENETICS, 2009, 41 (05) :527-534

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Erdmann, Jeanette ;

Grosshennig, Anika ;

Braund, Peter S. ;

Koenig, Inke R. ;

Hengstenberg, Christian ;

Hall, Alistair S. ;

Linsel-Nitschke, Patrick ;

Kathiresan, Sekar ;

Wright, Ben ;

Tregouet, David-Alexandre ;

Cambien, Francois ;

Bruse, Petra ;

Aherrahrou, Zouhair ;

Wagner, Arnika K. ;

Stark, Klaus ;

Schwartz, Stephen M. ;

Salomaa, Veikko ;

Elosua, Roberto ;

Melander, Olle ;

Voight, Benjamin F. ;

O'Donnell, Christopher J. ;

Peltonen, Leena ;

Siscovick, David S. ;

Altshuler, David ;

Merlini, Piera Angelica ;

Peyvandi, Flora ;

Bernardinelli, Luisa ;

Ardissino, Diego ;

Schillert, Arne ;

Blankenberg, Stefan ;

Zeller, Tanja ;

Wild, Philipp ;

Schwarz, Daniel F. ;

Tiret, Laurence ;

Perret, Claire ;

Schreiber, Stefan ;

El Mokhtari, Nour Eddine ;

Schaefer, Arne ;

Maerz, Winfried ;

Renner, Wilfried ;

Bugert, Peter ;

Klueter, Harald ;

Schrezenmeir, Juergen ;

Rubin, Diana ;

Ball, Stephen G. ;

Balmforth, Anthony J. ;

Wichmann, H-Erich ;

Meitinger, Thomas ;

Fischer, Marcus ;

Meisinger, Christa .

NATURE GENETICS, 2009, 41 (03) :280-282

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Gudbjartsson, Daniel F. ;

Bjornsdottir, Unnur S. ;

Halapi, Eva ;

Helgadottir, Anna ;

Sulem, Patrick ;

Jonsdottir, Gudrun M. ;

Thorleifsson, Gudmar ;

Helgadottir, Hafdis ;

Steinthorsdottir, Valgerdur ;

Stefansson, Hreinn ;

Williams, Carolyn ;

Hui, Jennie ;

Beilby, John ;

Warrington, Nicole M. ;

James, Alan ;

Palmer, Lyle J. ;

Koppelman, Gerard H. ;

Heinzmann, Andrea ;

Krueger, Marcus ;

Boezen, H. Marike ;

Wheatley, Amanda ;

Altmuller, Janine ;

Shin, Hyoung Doo ;

Uh, Soo-Taek ;

Cheong, Hyun Sub ;

Jonsdottir, Brynja ;

Gislason, David ;

Park, Choon-Sik ;

Rasmussen, Linda M. ;

Porsbjerg, Celeste ;

Hansen, Jakob W. ;

Backer, Vibeke ;

Werge, Thomas ;

Janson, Christer ;

Joensson, Ulla-Britt ;

Ng, Maggie C. Y. ;

Chan, Juliana ;

So, Wing Yee ;

Ma, Ronald ;

Shah, Svati H. ;

Granger, Christopher B. ;

Quyyumi, Arshed A. ;

Levey, Allan I. ;

Vaccarino, Viola ;

Reilly, Muredach P. ;

Rader, Daniel J. ;

Williams, Michael J. A. ;

van Rij, Andre M. ;

Jones, Gregory T. ;

Trabetti, Elisabetta .

NATURE GENETICS, 2009, 41 (03) :342-347

[6] FACTORS OF RISK IN DEVELOPMENT OF CORONARY HEART DISEASE - 6-YEAR FOLLOW-UP EXPERIENCE [J].

KANNEL, WB ;

KAGAN, A ;

STOKES, J ;

DAWBER, TR ;

REVOTSKIE, N .

ANNALS OF INTERNAL MEDICINE, 1961, 55 (01) :33-+

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Kathiresan, Sekar ;

Altschuler, David ;

Anand, Sonia ;

Ardissino, Diego ;

Asselta, Rosanna ;

Ball, Stephen G. ;

Balmforth, Anthony J. ;

Berger, Klaus ;

Berglund, Goran ;

Bernardi, Francesco ;

Bernardinelli, Luisa ;

Berzuini, Carlo ;

Braund, Peter S. ;

Burnett, Mary-Susan ;

Burtt, Noel ;

Cambien, Francois ;

Casari, Giorgio ;

Celli, Patrizia ;

Chen, Zhen ;

Corrocher, Roberto ;

Daly, Mark J. ;

Deloukas, Panos ;

Devaney, Joe ;

Do, Ron ;

Duga, Stefano ;

Elosua, Roberto ;

Engert, James C. ;

Epstein, Stephen E. ;

Erdmann, Jeanette ;

Ferrario, Maurizio ;

Fetiveau, Raffaela ;

Fischer, Marcus ;

Friedlander, Yechiel ;

Gabriel, Stacey B. ;

Galli, Michele ;

Gianniny, Lauren ;

Girelli, Domenico ;

Grosshennig, Anika ;

Guiducci, Candace ;

Hakonarson, Hakon H. ;

Hall, Alistair S. ;

Havulinna, Aki S. ;

Hengstenberg, Christian ;

Hirschhorn, Joel N. ;

Holm, Hilma ;

Huge, Andreas ;

Kent, Kenneth M. ;

Konig, Inke R. ;

Korn, Joshua M. ;

Li, Mingyao .

NATURE GENETICS, 2009, 41 (03) :334-341

[8] Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians [J].

Kato, Norihiro ;

Takeuchi, Fumihiko ;

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