Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

被引：62

作者：

Dehghan, Abbas ^{[1
]}

Bis, Joshua C. ^{[2
]}

White, Charles C. ^{[3
]}

Smith, Albert Vernon ^{[4
,5
]}

Morrison, Alanna C. ^{[6
,7
]}

Cupples, L. Adrienne ^{[3
,8
,9
]}

Trompet, Stella ^{[10
,11
]}

Chasman, Daniel I. ^{[12
,13
]}

Lumley, Thomas ^{[14
,15
]}

Voelker, Uwe ^{[16
,17
]}

Buckley, Brendan M. ^{[18
]}

Ding, Jingzhong ^{[19
]}

Jensen, Majken K. ^{[20
,21
]}

Folsom, Aaron R. ^{[22
]}

Kritchevsky, Stephen B. ^{[23
]}

Girman, Cynthia J. ^{[24
,25
]}

Ford, Ian ^{[26
]}

Doerr, Marcus ^{[17
,27
]}

Salomaa, Veikko ^{[28
]}

Uitterlinden, Andre G. ^{[1
,29
]}

Eiriksdottir, Gudny ^{[4
]}

Vasan, Ramachandran S. ^{[8
,9
,30
,31
,32
,33
]}

Franceschini, Nora ^{[24
]}

Carty, Cara L. ^{[34
]}

Virtamo, Jarmo ^{[28
]}

Demissie, Serkalem ^{[3
]}

Amouyel, Philippe ^{[35
]}

Arveiler, Dominique ^{[36
]}

Heckbert, Susan R. ^{[2
,37
,38
]}

Ferrieres, Jean ^{[39
,40
]}

Ducimetiere, Pierre ^{[41
]}

Smith, Nicholas L. ^{[37
,42
]}

Wang, Ying A. ^{[3
,43
]}

Siscovick, David S. ^{[44
]}

Rice, Kenneth M. ^{[14
]}

Wiklund, Per-Gunnar ^{[45
]}

Taylor, Kent D. ^{[46
,47
]}

Evans, Alun ^{[48
]}

Kee, Frank ^{[48
]}

Rotter, Jerome I. ^{[46
,47
]}

Karvanen, Juha ^{[28
,49
]}

Kuulasmaa, Kari ^{[28
]}

Heiss, Gerardo ^{[24
]}

Kraft, Peter ^{[50
]}

Launer, Lenore J. ^{[51
]}

Hofman, Albert ^{[1
]}

Markus, Marcello R. P. ^{[17
,52
]}

Rose, Lynda M. ^{[12
,13
]}

Silander, Kaisa ^{[28
,53
]}

Wagner, Peter ^{[28
,53
]}

机构：

[1] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[2] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[3] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[4] Icelandic Heart Assoc, Kopavogur, Iceland

[5] Univ Iceland, Reykjavik, Iceland

[6] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA

[7] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA

[8] Boston Univ, Framingham, MA USA

[9] NHLBI, Framingham Heart Study, Framingham, MA USA

[10] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands

[11] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands

[12] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[13] Harvard Univ, Sch Med, Boston, MA USA

[14] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[15] Univ Auckland, Dept Stat, Auckland 1, New Zealand

[16] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[17] DZHK German Ctr Cardiovasc Res, Partner Site, Greifswald, Germany

[18] Univ Coll, Dept Pharmacol & Therapeut, Cork, Ireland

[19] Wake Forest Univ, Dept Internal Med, Div Geriatr, Winston Salem, NC 27109 USA

[20] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[21] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA

[22] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[23] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA

[24] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA

[25] Merck Sharp & Dohme Corp, Dept Epidemiol, Merck Res Labs, Whitehouse Stn, NJ USA

[26] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland

[27] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany

[28] Natl Inst Hlth & Welf, Helsinki, Finland

[29] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[30] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[31] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[32] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA

[33] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA

[34] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[35] Inst Pasteur, Dept Epidemiol & Publ Hlth, F-59019 Lille, France

[36] Univ Strasbourg, Dept Epidemiol & Publ Hlth, EA 3430, Strasbourg, France

[37] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[38] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA

[39] Toulouse Univ Hosp, Dept Cardiol, Toulouse, France

[40] Toulouse Univ Hosp, Dept Epidemiol, Toulouse, France

[41] Natl Inst Hlth & Med Res, U258, Paris, France

[42] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA

[43] Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA USA

[44] New York Acad Med, New York, NY USA

[45] Umea Univ Hosp, Dept Med, S-90185 Umea, Sweden

[46] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA

[47] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA

[48] Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res Northern Irela, Belfast, Antrim, North Ireland

[49] Univ Jyvaskyla, Dept Math & Stat, Jyvaskyla, Finland

[50] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

来源：

PLOS ONE | 2016年 / 11卷 / 03期

关键词：

CHROMOSOME; 9P21; RISK; DESIGN; SUSCEPTIBILITY; PREDICTION;

D O I：

10.1371/journal.pone.0144997

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5x10(-6) in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5x10(-6); 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8x10(-3)) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2x10(-9)). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2x10(-3)). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.

引用

页数：16

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