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Lancet. 2011 Jan 29;377(9763):383-92. doi: 10.1016/S0140-6736(10)61996-4. Epub 2011 Jan 14.

Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.

Collaborators (391)

Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Thompson JR, Braund PS, Wright B, Balmforth AJ, Ball SG, Hall AS, Samani NJ, Stewart AF, Chen L, Wells GA, McPherson R, Roberts R, Wild PS, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Blankenberg S, Assimes TL, Absher D, Hlatky MA, Iribaren C, Knowles JW, Quertermous T, Kathiresan S, Linsel-Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Erdmann J, Schunkert H, Patel RS, Su S, Bouzyk M, Vaccarino V, Zafari AM, Quyyumi AA, Horne BD, Carlquist JF, Muhlestein JB, Anderson JL, Martinelli N, Olivieri O, Girelli D, Barnard J, Allayee H, Hartiala J, Tang WH, Hazen SL, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Burton PR, Davison D, Donnelly P, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Cardon LR, Clayton DG, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Todd JA, Ouwehand WH, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Craddock N, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Burton PR, Dixon RJ, Mangino M, Stevens S, Tobin MD, Thompson JR, Samani NJ, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Clayton DG, Lathrop M, Connell J, Dominiczak A, Samani NJ, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Clayton DG, Dunger DB, Nutland S, Stevens HE, Walker NM, Widmer B, Todd JA, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, McCarthy MI, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Newport M, Sirugo G, Rockett KA, Kwiatkowski DP, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Deloukas P, Leung HT, Nutland S, Stevens HE, Walker NM, Todd JA, Easton D, Clayton DG, Burton PR, Tobin MD, Barrett JC, Evans DM, Morris AP, Cardon LR, Cardin NJ, Davison D, Ferreira T, Pereira-Gale J, Hallgrimsdóttir IB, Bowie BN, Marchini JL, Spencer CC, Su Z, Teo YY, Vukcevic D, Donnelly P, Bentley D, Brown MA, Cardon LR, Caulfield M, Clayton DG, Compston A, Craddock N, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Samani NJ, Stratton MR, Todd JA, Worthington J, Kathiresan S, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Kathiresan S, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Schwartz SM, Yee J, Kathiresan S, Lucas G, Subirana I, Elosua R, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB.

Abstract

BACKGROUND:

We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.

METHODS:

We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644).

FINDINGS:

In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction.

INTERPRETATION:

Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD.

FUNDING:

The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.

Copyright © 2011 Elsevier Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
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