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

Reilly, M.P.; Li, M.; He, J.; Ferguson, J.F.; Stylianou, I.M.; Mehta, N.N.; Burnett, M.S.; Devaney, J.M.; Knouff, C.W.; Thompson, J.R.; Horne, B.D.; Stewart, A.F.; Assimes, T.L.; Wild, P.S.; Allayee, H.; Nitschke, P.L.; Patel, R.S.; Mi Genetics Consortium,; Wellcome Trust Case Control Consortium,; Martinelli, N.; Girelli, D.; Quyyumi, A.A.; Anderson, J.L.; Erdmann, J.; Hall, A.S.; Schunkert, H.; Quertermous, T.; Blankenberg, S.; Hazen, S.L.; Roberts, R.; Kathiresan, S.; Samani, N.J.; Epstein, S.E.; Rader, D.J.; Qasim, A.N.; Derohannessian, S.L.; Qu, L.; Cappola, T.P.; Chen, Z.; Matthai, W.; Hakonarson, H.H.; Wilensky, R.; Kent, K.M.; Lindsay, J.M.; Pichard, A.D.; Satler, L.; Waksman, R.; Knoupf, C.W.; Walker, M.C.; Waterworth, D.M.; Mosser, V.; Thompson, J.R.; Braund, P.S.; Wright, B.; Balmforth, A.J.; Ball, S.G.; Hall, A.S.; Samani, N.J.; Stewart, A.F.; Chen, L.; Wells, G.A.; Mcpherson, R.; Roberts, R.; Wild, P.S.; Lackner, K.; Munzel, T.F.; Schillert, A.; Schnabel, R.; Zeller, T.; Ziegler, A.; Blankenberg, S.; Assimes, T.L.; Absher, D.; Hlatky, M.A.; Iribaren, C.; Knowles, J.W.; Quertermous, T.; Kathiresan, S.; Linsel Nitschke, P.; König, I.R.; Hengstenberg, C.; Nahrstaedt, J.; Peters, A.; Schreiber, S.; Wichmann, E.; Willenborg, C.; Erdmann, J.; Schunkert, H.; Patel, R.S.; Su, S.; Bouzyk, M.; Vaccarino, V.; Zafari, A.M.; Quyyumi, A.A.; Horne, B.D.; Carlquist, J.F.; Muhlestein, J.B.; Anderson, J.L.; Martinelli, N.; Olivieri, O.; Girelli, D.; Barnard, J.; Allayee, H.; Hartiala, J.; Tang, W.H.; Hazen, S.L.; Burton, P.R.; Clayton, D.G.; Cardon, L.R.; Craddock, N.; Deloukas, P.; Duncanson, A.; Kwiatkowski, D.P.; Mccarthy, M.I.; Ouwehand, W.H.; Samani, N.J.; Todd, J.A.; Donnelly, P.; Barrett, J.C.; Burton, P.R.; Davison, D.; Donnelly, P.; Easton, D.; Evans, D.M.; Leung, H.T.; Marchini, J.L.; Morris, A.P.; Spencer, C.C.; Tobin, M.D.; Cardon, L.R.; Clayton, D.G.; Attwood, A.P.; Boorman, J.P.; Cant, B.; Everson, U.; Hussey, J.M.; Jolley, J.D.; Knight, A.S.; Koch, K.; Meech, E.; Nutland, S.; Prowse, C.V.; Stevens, H.E.; Taylor, N.C.; Walters, G.R.; Walker, N.M.; Watkins, N.A.; Winzer, T.; Todd, J.A.; Ouwehand, W.H.; Jones, R.W.; Mcardle, W.L.; Ring, S.M.; Strachan, D.P.; Pembrey, M.; Breen, G.; St Clair, D.; Caesar, S.; Gordon Smith, K.; Jones, L.; Fraser, C.; Green, E.K.; Grozeva, D.; Hamshere, M.L.; Holmans, P.A.; Jones, I.R.; Kirov, G.; Moskvina, V.; Nikolov, I.; O'Donovan, M.C.; Owen, M.J.; Craddock, N.; Collier, D.A.; Elkin, A.; Farmer, A.; Williamson, R.; Mcguffin, P.; Young, A.H.; Ferrier, I.N.; Ball, S.G.; Balmforth, A.J.; Barrett, J.H.; Bishop, D.T.; Iles, M.M.; Maqbool, A.; Yuldasheva, N.; Hall, A.S.; Braund, P.S.; Burton, P.R.; Dixon, R.J.; Mangino, M.; Stevens, S.; Tobin, M.D.; Thompson, J.R.; Samani, N.J.; Bredin, F.; Tremelling, M.; Parkes, M.; Drummond, H.; Lees, C.W.; Nimmo, E.R.; Satsangi, J.; Fisher, S.A.; Forbes, A.; Lewis, C.M.; Onnie, C.M.; Prescott, N.J.; Sanderson, J.; Mathew, C.G.; Barbour, J.; Mohiuddin, M.K.; Todhunter, C.E.; Mansfield, J.C.; Ahmad, T.; Cummings, F.R.; Jewell, D.P.; Webster, J.; Brown, M.J.; Clayton, D.G.; Lathrop, M.; Connell, J.; Dominiczak, A.; Samani, N.J.; Marcano, C.A.; Burke, B.; Dobson, R.; Gungadoo, J.; Lee, K.L.; Munroe, P.B.; Newhouse, S.J.; Onipinla, A.; Wallace, C.; Xue, M.; Caulfield, M.; Farrall, M.; Barton, A.; Bruce, I.N.; Donovan, H.; Eyre, S.; Gilbert, P.D.; Hider, S.L.; Hinks, A.M.; John, S.L.; Potter, C.; Silman, A.J.; Symmons, D.P.; Thomson, W.; Worthington, J.; Clayton, D.G.; Dunger, D.B.; Nutland, S.; Stevens, H.E.; Walker, N.M.; Widmer, B.; Todd, J.A.; Frayling, T.M.; Freathy, R.M.; Lango, H.; Perry, J.R.; Shields, B.M.; Weedon, M.N.; Hattersley, A.T.; Hitman, G.A.; Walker, M.; Elliott, K.S.; Groves, C.J.; Lindgren, C.M.; Rayner, N.W.; Timpson, N.J.; Zeggini, E.; Mccarthy, M.I.; Newport, M.; Sirugo, G.; Lyons, E.; Vannberg, F.; Hill, A.V.; Bradbury, L.A.; Farrar, C.; Pointon, J.J.; Wordsworth, P.; Brown, M.A.; Franklyn, J.A.; Heward, J.M.; Simmonds, M.J.; Gough, S.C.; Seal, S.; Stratton, M.R.; Rahman, N.; Ban, M.; Goris, A.; Sawcer, S.J.; Compston, A.; Conway, D.; Jallow, M.; Newport, M.; Sirugo, G.; Rockett, K.A.; Kwiatkowski, D.P.; Bumpstead, S.J.; Chaney, A.; Downes, K.; Ghori, M.J.; Gwilliam, R.; Hunt, S.E.; Inouye, M.; Keniry, A.; King, E.; Mcginnis, R.; Potter, S.; Ravindrarajah, R.; Whittaker, P.; Widden, C.; Withers, D.; Deloukas, P.; Leung, H.T.; Nutland, S.; Stevens, H.E.; Walker, N.M.; Todd, J.A.; Easton, D.; Clayton, D.G.; Burton, P.R.; Tobin, M.D.; Barrett, J.C.; Evans, D.M.; Morris, A.P.; Cardon, L.R.; Cardin, N.J.; Davison, D.; Ferreira, T.; Pereira Gale, J.; Hallgrimsdóttir, I.B.; Bowie, B.N.; Marchini, J.L.; Spencer, C.C.; Su, Z.; Teo, Y.Y.; Vukcevic, D.; Donnelly, P.; Bentley, D.; Brown, M.A.; Cardon, L.R.; Caulfield, M.; Clayton, D.G.; Compston, A.; Craddock, N.; Deloukas, P.; Donnelly, P.; Farrall, M.; Gough, S.C.; Hall, A.S.; Hattersley, A.T.; Hill, A.V.; Kwiatkowski, D.P.; Mathew, C.G.; Mccarthy, M.I.; Ouwehand, W.H.; Parkes, M.; Pembrey, M.; Rahman, N.; Samani, N.J.; Stratton, M.R.; Todd, J.A.; Worthington, J.; Kathiresan, S.; Meigs, J.B.; Williams, G.; Nathan, D.M.; Macrae, C.A.; O'Donnell, C.J.; Ardissino, D.; Merlini, P.A.; 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, P.M.; Schwartz, S.M.; Siscovick, D.S.; Yee, J.; Friedlander, Y.; Elosua, R.; Marrugat, J.; Lucas, G.; Subirana, I.; Sala, J.; Ramos, R.; Salomaa, V.; Havulinna, A.S.; Peltonen, L.; Melander, O.; Berglund, G.; Voight, B.F.; Kathiresan, S.; Hirschhorn, J.N.; Asselta, R.; Duga, S.; Spreafico, M.; Musunuru, K.; Daly, M.J.; Purcell, S.; Schwartz, S.M.; Yee, J.; Kathiresan, S.; Lucas, G.; Subirana, I.; Elosua, R.; Surti, A.; Guiducci, C.; Gianniny, L.; Mirel, D.; Parkin, M.; Burtt, N.; Gabriel, S.B.

doi:10.1016/S0140-6736(10)61996-4

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.

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 / MP. Reilly, M. Li, J. He, JF. Ferguson, IM. Stylianou, NN. Mehta, MS. Burnett, JM. Devaney, CW. Knouff, JR. Thompson, BD. Horne, AF. Stewart, TL. Assimes, PS. Wild, H. Allayee, PL. Nitschke, RS. Patel, MI Genetics Consortium, Wellcome Trust Case Control Consortium, N. Martinelli, D. Girelli, AA. Quyyumi, JL. Anderson, J. Erdmann, AS. Hall, H. Schunkert, T. Quertermous, S. Blankenberg, SL. Hazen, R. Roberts, S. Kathiresan, NJ. Samani, SE. Epstein, DJ. Rader, AN. Qasim, SL. DerOhannessian, L. Qu, TP. Cappola, Z. Chen, W. Matthai, HH. Hakonarson, R. Wilensky, KM. Kent, JM. Lindsay, AD. Pichard, L. Satler, R. Waksman, CW. Knoupf, MC. Walker, DM. Waterworth, V. Mosser, JR. Thompson, PS. Braund, B. Wright, AJ. Balmforth, SG. Ball, AS. Hall, NJ. Samani, AF. Stewart, L. Chen, GA. Wells, R. McPherson, R. Roberts, PS. Wild, K. Lackner, TF. Munzel, A. Schillert, R. Schnabel, T. Zeller, A. Ziegler, S. Blankenberg, TL. Assimes, D. Absher, MA. Hlatky, C. Iribaren, JW. Knowles, T. Quertermous, S. Kathiresan, P. Linsel-Nitschke, IR. König, C. Hengstenberg, J. Nahrstaedt, A. Peters, S. Schreiber, E. Wichmann, C. Willenborg, J. Erdmann, H. Schunkert, RS. Patel, S. Su, M. Bouzyk, V. Vaccarino, AM. Zafari, AA. Quyyumi, BD. Horne, JF. Carlquist, JB. Muhlestein, JL. Anderson, N. Martinelli, O. Olivieri, D. Girelli, J. Barnard, H. Allayee, J. Hartiala, WH. Tang, SL. Hazen, PR. Burton, DG. Clayton, LR. Cardon, N. Craddock, P. Deloukas, A. Duncanson, DP. Kwiatkowski, MI. McCarthy, WH. Ouwehand, NJ. Samani, JA. Todd, P. Donnelly, JC. Barrett, PR. Burton, D. Davison, P. Donnelly, D. Easton, DM. Evans, HT. Leung, JL. Marchini, AP. Morris, CC. Spencer, MD. Tobin, LR. Cardon, DG. Clayton, AP. Attwood, JP. Boorman, B. Cant, U. Everson, JM. Hussey, JD. Jolley, AS. Knight, K. Koch, E. Meech, S. Nutland, CV. Prowse, HE. Stevens, NC. Taylor, GR. Walters, NM. Walker, NA. Watkins, T. Winzer, JA. Todd, WH. Ouwehand, RW. Jones, WL. McArdle, SM. Ring, DP. Strachan, M. Pembrey, G. Breen, D. St Clair, S. Caesar, K. Gordon-Smith, L. Jones, C. Fraser, EK. Green, D. Grozeva, ML. Hamshere, PA. Holmans, IR. Jones, G. Kirov, V. Moskvina, I. Nikolov, MC. O'Donovan, MJ. Owen, N. Craddock, DA. Collier, A. Elkin, A. Farmer, R. Williamson, P. McGuffin, AH. Young, IN. Ferrier, SG. Ball, AJ. Balmforth, JH. Barrett, DT. Bishop, MM. Iles, A. Maqbool, N. Yuldasheva, AS. Hall, PS. Braund, PR. Burton, RJ. Dixon, M. Mangino, S. Stevens, MD. Tobin, JR. Thompson, NJ. Samani, F. Bredin, M. Tremelling, M. Parkes, H. Drummond, CW. Lees, ER. Nimmo, J. Satsangi, SA. Fisher, A. Forbes, CM. Lewis, CM. Onnie, NJ. Prescott, J. Sanderson, CG. Mathew, J. Barbour, MK. Mohiuddin, CE. Todhunter, JC. Mansfield, T. Ahmad, FR. Cummings, DP. Jewell, J. Webster, MJ. Brown, DG. Clayton, M. Lathrop, J. Connell, A. Dominiczak, NJ. Samani, CA. Marcano, B. Burke, R. Dobson, J. Gungadoo, KL. Lee, PB. Munroe, SJ. Newhouse, A. Onipinla, C. Wallace, M. Xue, M. Caulfield, M. Farrall, A. Barton, IN. Bruce, H. Donovan, S. Eyre, PD. Gilbert, SL. Hider, AM. Hinks, SL. John, C. Potter, AJ. Silman, DP. Symmons, W. Thomson, J. Worthington, DG. Clayton, DB. Dunger, S. Nutland, HE. Stevens, NM. Walker, B. Widmer, JA. Todd, TM. Frayling, RM. Freathy, H. Lango, JR. Perry, BM. Shields, MN. Weedon, AT. Hattersley, GA. Hitman, M. Walker, KS. Elliott, CJ. Groves, CM. Lindgren, NW. Rayner, NJ. Timpson, E. Zeggini, MI. McCarthy, M. Newport, G. Sirugo, E. Lyons, F. Vannberg, AV. Hill, LA. Bradbury, C. Farrar, JJ. Pointon, P. Wordsworth, MA. Brown, JA. Franklyn, JM. Heward, MJ. Simmonds, SC. Gough, S. Seal, MR. Stratton, N. Rahman, M. Ban, A. Goris, SJ. Sawcer, A. Compston, D. Conway, M. Jallow, M. Newport, G. Sirugo, KA. Rockett, DP. Kwiatkowski, SJ. Bumpstead, A. Chaney, K. Downes, MJ. Ghori, R. Gwilliam, SE. Hunt, M. Inouye, A. Keniry, E. King, R. McGinnis, S. Potter, R. Ravindrarajah, P. Whittaker, C. Widden, D. Withers, P. Deloukas, HT. Leung, S. Nutland, HE. Stevens, NM. Walker, JA. Todd, D. Easton, DG. Clayton, PR. Burton, MD. Tobin, JC. Barrett, DM. Evans, AP. Morris, LR. Cardon, NJ. Cardin, D. Davison, T. Ferreira, J. Pereira-Gale, IB. Hallgrimsdóttir, BN. Bowie, JL. Marchini, CC. Spencer, Z. Su, YY. Teo, D. Vukcevic, P. Donnelly, D. Bentley, MA. Brown, LR. Cardon, M. Caulfield, DG. Clayton, A. Compston, N. Craddock, P. Deloukas, P. Donnelly, M. Farrall, SC. Gough, AS. Hall, AT. Hattersley, AV. Hill, DP. Kwiatkowski, CG. Mathew, MI. McCarthy, WH. Ouwehand, M. Parkes, M. Pembrey, N. Rahman, NJ. Samani, MR. Stratton, JA. Todd, J. Worthington, S. Kathiresan, JB. Meigs, G. Williams, DM. Nathan, CA. MacRae, CJ. O'Donnell, D. Ardissino, PA. Merlini, C. Berzuini, L. Bernardinelli, F. Peyvandi, M. Tubaro, P. Celli, M. Ferrario, R. Fetiveau, N. Marziliano, G. Casari, M. Galli, F. Ribichini, M. Rossi, F. Bernardi, P. Zonzin, A. Piazza, PM. Mannucci, SM. Schwartz, DS. Siscovick, J. Yee, Y. Friedlander, R. Elosua, J. Marrugat, G. Lucas, I. Subirana, J. Sala, R. Ramos, V. Salomaa, AS. Havulinna, L. Peltonen, O. Melander, G. Berglund, BF. Voight, S. Kathiresan, JN. Hirschhorn, R. Asselta, S. Duga, M. Spreafico, K. Musunuru, MJ. Daly, S. Purcell, SM. Schwartz, J. Yee, S. Kathiresan, G. Lucas, I. Subirana, R. Elosua, A. Surti, C. Guiducci, L. Gianniny, D. Mirel, M. Parkin, N. Burtt, SB. Gabriel. - In: THE LANCET. - ISSN 0140-6736. - 377:9763(2011 Jan 29), pp. 383-392. [10.1016/S0140-6736(10)61996-4]

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

M.P. Reilly;M. Li;J. He;J.F. Ferguson;I.M. Stylianou;N.N. Mehta;M.S. Burnett;J.M. Devaney;C.W. Knouff;J.R. Thompson;B.D. Horne;A.F. Stewart;T.L. Assimes;P.S. Wild;H. Allayee;P.L. Nitschke;R.S. Patel;MI Genetics Consortium;Wellcome Trust Case Control Consortium;N. Martinelli;D. Girelli;A.A. Quyyumi;J.L. Anderson;J. Erdmann;A.S. Hall;H. Schunkert;T. Quertermous;S. Blankenberg;S.L. Hazen;R. Roberts;S. Kathiresan;N.J. Samani;S.E. Epstein;D.J. Rader;A.N. Qasim;S.L. DerOhannessian;L. Qu;T.P. Cappola;Z. Chen;W. Matthai;H.H. Hakonarson;R. Wilensky;K.M. Kent;J.M. Lindsay;A.D. Pichard;L. Satler;R. Waksman;C.W. Knoupf;M.C. Walker;D.M. Waterworth;V. Mosser;J.R. Thompson;P.S. Braund;B. Wright;A.J. Balmforth;S.G. Ball;A.S. Hall;N.J. Samani;A.F. Stewart;L. Chen;G.A. Wells;R. McPherson;R. Roberts;P.S. Wild;K. Lackner;T.F. Munzel;A. Schillert;R. Schnabel;T. Zeller;A. Ziegler;S. Blankenberg;T.L. Assimes;D. Absher;M.A. Hlatky;C. Iribaren;J.W. Knowles;T. Quertermous;S. Kathiresan;P. Linsel Nitschke;I.R. König;C. Hengstenberg;J. Nahrstaedt;A. Peters;S. Schreiber;E. Wichmann;C. Willenborg;J. Erdmann;H. Schunkert;R.S. Patel;S. Su;M. Bouzyk;V. Vaccarino;A.M. Zafari;A.A. Quyyumi;B.D. Horne;J.F. Carlquist;J.B. Muhlestein;J.L. Anderson;N. Martinelli;O. Olivieri;D. Girelli;J. Barnard;H. Allayee;J. Hartiala;W.H. Tang;S.L. Hazen;P.R. Burton;D.G. Clayton;L.R. Cardon;N. Craddock;P. Deloukas;A. Duncanson;D.P. Kwiatkowski;M.I. McCarthy;W.H. Ouwehand;N.J. Samani;J.A. Todd;P. Donnelly;J.C. Barrett;P.R. Burton;D. Davison;P. Donnelly;D. Easton;D.M. Evans;H.T. Leung;J.L. Marchini;A.P. Morris;C.C. Spencer;M.D. Tobin;L.R. Cardon;D.G. Clayton;A.P. Attwood;J.P. Boorman;B. Cant;U. Everson;J.M. Hussey;J.D. Jolley;A.S. Knight;K. Koch;E. Meech;S. Nutland;C.V. Prowse;H.E. Stevens;N.C. Taylor;G.R. Walters;N.M. Walker;N.A. Watkins;T. Winzer;J.A. Todd;W.H. Ouwehand;R.W. Jones;W.L. McArdle;S.M. Ring;D.P. Strachan;M. Pembrey;G. Breen;D. St Clair;S. Caesar;K. Gordon Smith;L. Jones;C. Fraser;E.K. Green;D. Grozeva;M.L. Hamshere;P.A. Holmans;I.R. Jones;G. Kirov;V. Moskvina;I. Nikolov;M.C. O'Donovan;M.J. Owen;N. Craddock;D.A. Collier;A. Elkin;A. Farmer;R. Williamson;P. McGuffin;A.H. Young;I.N. Ferrier;S.G. Ball;A.J. Balmforth;J.H. Barrett;D.T. Bishop;M.M. Iles;A. Maqbool;N. Yuldasheva;A.S. Hall;P.S. Braund;P.R. Burton;R.J. Dixon;M. Mangino;S. Stevens;M.D. Tobin;J.R. Thompson;N.J. Samani;F. Bredin;M. Tremelling;M. Parkes;H. Drummond;C.W. Lees;E.R. Nimmo;J. Satsangi;S.A. Fisher;A. Forbes;C.M. Lewis;C.M. Onnie;N.J. Prescott;J. Sanderson;C.G. Mathew;J. Barbour;M.K. Mohiuddin;C.E. Todhunter;J.C. Mansfield;T. Ahmad;F.R. Cummings;D.P. Jewell;J. Webster;M.J. Brown;D.G. Clayton;M. Lathrop;J. Connell;A. Dominiczak;N.J. Samani;C.A. Marcano;B. Burke;R. Dobson;J. Gungadoo;K.L. Lee;P.B. Munroe;S.J. Newhouse;A. Onipinla;C. Wallace;M. Xue;M. Caulfield;M. Farrall;A. Barton;I.N. Bruce;H. Donovan;S. Eyre;P.D. Gilbert;S.L. Hider;A.M. Hinks;S.L. John;C. Potter;A.J. Silman;D.P. Symmons;W. Thomson;J. Worthington;D.G. Clayton;D.B. Dunger;S. Nutland;H.E. Stevens;N.M. Walker;B. Widmer;J.A. Todd;T.M. Frayling;R.M. Freathy;H. Lango;J.R. Perry;B.M. Shields;M.N. Weedon;A.T. Hattersley;G.A. Hitman;M. Walker;K.S. Elliott;C.J. Groves;C.M. Lindgren;N.W. Rayner;N.J. Timpson;E. Zeggini;M.I. McCarthy;M. Newport;G. Sirugo;E. Lyons;F. Vannberg;A.V. Hill;L.A. Bradbury;C. Farrar;J.J. Pointon;P. Wordsworth;M.A. Brown;J.A. Franklyn;J.M. Heward;M.J. Simmonds;S.C. Gough;S. Seal;M.R. Stratton;N. Rahman;M. Ban;A. Goris;S.J. Sawcer;A. Compston;D. Conway;M. Jallow;M. Newport;G. Sirugo;K.A. Rockett;D.P. Kwiatkowski;S.J. Bumpstead;A. Chaney;K. Downes;M.J. Ghori;R. Gwilliam;S.E. Hunt;M. Inouye;A. Keniry;E. King;R. McGinnis;S. Potter;R. Ravindrarajah;P. Whittaker;C. Widden;D. Withers;P. Deloukas;H.T. Leung;S. Nutland;H.E. Stevens;N.M. Walker;J.A. Todd;D. Easton;D.G. Clayton;P.R. Burton;M.D. Tobin;J.C. Barrett;D.M. Evans;A.P. Morris;L.R. Cardon;N.J. Cardin;D. Davison;T. Ferreira;J. Pereira Gale;I.B. Hallgrimsdóttir;B.N. Bowie;J.L. Marchini;C.C. Spencer;Z. Su;Y.Y. Teo;D. Vukcevic;P. Donnelly;D. Bentley;M.A. Brown;L.R. Cardon;M. Caulfield;D.G. Clayton;A. Compston;N. Craddock;P. Deloukas;P. Donnelly;M. Farrall;S.C. Gough;A.S. Hall;A.T. Hattersley;A.V. Hill;D.P. Kwiatkowski;C.G. Mathew;M.I. McCarthy;W.H. Ouwehand;M. Parkes;M. Pembrey;N. Rahman;N.J. Samani;M.R. Stratton;J.A. Todd;J. Worthington;S. Kathiresan;J.B. Meigs;G. Williams;D.M. Nathan;C.A. MacRae;C.J. O'Donnell;D. Ardissino;P.A. Merlini;C. Berzuini;L. Bernardinelli;F. Peyvandi;M. Tubaro;P. Celli;M. Ferrario;R. Fetiveau;N. Marziliano;G. Casari;M. Galli;F. Ribichini;M. Rossi;F. Bernardi;P. Zonzin;A. Piazza;P.M. Mannucci;S.M. Schwartz;D.S. Siscovick;J. Yee;Y. Friedlander;R. Elosua;J. Marrugat;G. Lucas;I. Subirana;J. Sala;R. Ramos;V. Salomaa;A.S. Havulinna;L. Peltonen;O. Melander;G. Berglund;B.F. Voight;S. Kathiresan;J.N. Hirschhorn;R. Asselta;S. Duga;M. Spreafico;K. Musunuru;M.J. Daly;S. Purcell;S.M. Schwartz;J. Yee;S. Kathiresan;G. Lucas;I. Subirana;R. Elosua;A. Surti;C. Guiducci;L. Gianniny;D. Mirel;M. Parkin;N. Burtt;S.B. Gabriel

2011

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.

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	Presenza di coautori internazionali
	
				No
			
	Lingua dell'articolo
	
				English
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore BIO/11 - Biologia Molecolare
Settore MED/09 - Medicina Interna
			
	Tipo
	
				Articolo
			
	Revisione (peer review)
	
				Esperti anonimi
			
	Classificazione della pubblicazione
	
				Pubblicazione scientifica
			
	Data di pubblicazione
	
				29-gen-2011
			
	Rivista in ANCE
	
				THE LANCET
			
	Volume o annata
	
				377
			
	Fascicolo
	
				9763
			
	Pagina iniziale
	
				383
			
	Pagina finale
	
				392
			
	Numero di pagine
	
				10
			
	Stato di pubblicazione
	
				Pubblicato
			
	Rilevanza del periodico
	
				Periodico con rilevanza internazionale
			
	DOI
	
				https://dx.doi.org/10.1016/S0140-6736(10)61996-4
			
	Identificativo ISI
	
				WOS:000287337000028
			
	Identificativo SCOPUS
	
				2-s2.0-79251619566
			
	Identificativo PUBMED
	
				21239051
			
	Adesione alla policy Open Access di Ateneo
	
				Aderisco
			
	Tipologia
	
				info:eu-repo/semantics/article
			
	Citazione
	
				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 / MP. Reilly, M. Li, J. He, JF. Ferguson, IM. Stylianou, NN. Mehta, MS. Burnett, JM. Devaney, CW. Knouff, JR. Thompson, BD. Horne, AF. Stewart, TL. Assimes, PS. Wild, H. Allayee, PL. Nitschke, RS. Patel, MI Genetics Consortium, Wellcome Trust Case Control Consortium, N. Martinelli, D. Girelli, AA. Quyyumi, JL. Anderson, J. Erdmann, AS. Hall, H. Schunkert, T. Quertermous, S. Blankenberg, SL. Hazen, R. Roberts, S. Kathiresan, NJ. Samani, SE. Epstein, DJ. Rader, AN. Qasim, SL. DerOhannessian, L. Qu, TP. Cappola, Z. Chen, W. Matthai, HH. Hakonarson, R. Wilensky, KM. Kent, JM. Lindsay, AD. Pichard, L. Satler, R. Waksman, CW. Knoupf, MC. Walker, DM. Waterworth, V. Mosser, JR. Thompson, PS. Braund, B. Wright, AJ. Balmforth, SG. Ball, AS. Hall, NJ. Samani, AF. Stewart, L. Chen, GA. Wells, R. McPherson, R. Roberts, PS. Wild, K. Lackner, TF. Munzel, A. Schillert, R. Schnabel, T. Zeller, A. Ziegler, S. Blankenberg, TL. Assimes, D. Absher, MA. Hlatky, C. Iribaren, JW. Knowles, T. Quertermous, S. Kathiresan, P. Linsel-Nitschke, IR. König, C. Hengstenberg, J. Nahrstaedt, A. Peters, S. Schreiber, E. Wichmann, C. Willenborg, J. Erdmann, H. Schunkert, RS. Patel, S. Su, M. Bouzyk, V. Vaccarino, AM. Zafari, AA. Quyyumi, BD. Horne, JF. Carlquist, JB. Muhlestein, JL. Anderson, N. Martinelli, O. Olivieri, D. Girelli, J. Barnard, H. Allayee, J. Hartiala, WH. Tang, SL. Hazen, PR. Burton, DG. Clayton, LR. Cardon, N. Craddock, P. Deloukas, A. Duncanson, DP. Kwiatkowski, MI. McCarthy, WH. Ouwehand, NJ. Samani, JA. Todd, P. Donnelly, JC. Barrett, PR. Burton, D. Davison, P. Donnelly, D. Easton, DM. Evans, HT. Leung, JL. Marchini, AP. Morris, CC. Spencer, MD. Tobin, LR. Cardon, DG. Clayton, AP. Attwood, JP. Boorman, B. Cant, U. Everson, JM. Hussey, JD. Jolley, AS. Knight, K. Koch, E. Meech, S. Nutland, CV. Prowse, HE. Stevens, NC. Taylor, GR. Walters, NM. Walker, NA. Watkins, T. Winzer, JA. Todd, WH. Ouwehand, RW. Jones, WL. McArdle, SM. Ring, DP. Strachan, M. Pembrey, G. Breen, D. St Clair, S. Caesar, K. Gordon-Smith, L. Jones, C. Fraser, EK. Green, D. Grozeva, ML. Hamshere, PA. Holmans, IR. Jones, G. Kirov, V. Moskvina, I. Nikolov, MC. O'Donovan, MJ. Owen, N. Craddock, DA. Collier, A. Elkin, A. Farmer, R. Williamson, P. McGuffin, AH. Young, IN. Ferrier, SG. Ball, AJ. Balmforth, JH. Barrett, DT. Bishop, MM. Iles, A. Maqbool, N. Yuldasheva, AS. Hall, PS. Braund, PR. Burton, RJ. Dixon, M. Mangino, S. Stevens, MD. Tobin, JR. Thompson, NJ. Samani, F. Bredin, M. Tremelling, M. Parkes, H. Drummond, CW. Lees, ER. Nimmo, J. Satsangi, SA. Fisher, A. Forbes, CM. Lewis, CM. Onnie, NJ. Prescott, J. Sanderson, CG. Mathew, J. Barbour, MK. Mohiuddin, CE. Todhunter, JC. Mansfield, T. Ahmad, FR. Cummings, DP. Jewell, J. Webster, MJ. Brown, DG. Clayton, M. Lathrop, J. Connell, A. Dominiczak, NJ. Samani, CA. Marcano, B. Burke, R. Dobson, J. Gungadoo, KL. Lee, PB. Munroe, SJ. Newhouse, A. Onipinla, C. Wallace, M. Xue, M. Caulfield, M. Farrall, A. Barton, IN. Bruce, H. Donovan, S. Eyre, PD. Gilbert, SL. Hider, AM. Hinks, SL. John, C. Potter, AJ. Silman, DP. Symmons, W. Thomson, J. Worthington, DG. Clayton, DB. Dunger, S. Nutland, HE. Stevens, NM. Walker, B. Widmer, JA. Todd, TM. Frayling, RM. Freathy, H. Lango, JR. Perry, BM. Shields, MN. Weedon, AT. Hattersley, GA. Hitman, M. Walker, KS. Elliott, CJ. Groves, CM. Lindgren, NW. Rayner, NJ. Timpson, E. Zeggini, MI. McCarthy, M. Newport, G. Sirugo, E. Lyons, F. Vannberg, AV. Hill, LA. Bradbury, C. Farrar, JJ. Pointon, P. Wordsworth, MA. Brown, JA. Franklyn, JM. Heward, MJ. Simmonds, SC. Gough, S. Seal, MR. Stratton, N. Rahman, M. Ban, A. Goris, SJ. Sawcer, A. Compston, D. Conway, M. Jallow, M. Newport, G. Sirugo, KA. Rockett, DP. Kwiatkowski, SJ. Bumpstead, A. Chaney, K. Downes, MJ. Ghori, R. Gwilliam, SE. Hunt, M. Inouye, A. Keniry, E. King, R. McGinnis, S. Potter, R. Ravindrarajah, P. Whittaker, C. Widden, D. Withers, P. Deloukas, HT. Leung, S. Nutland, HE. Stevens, NM. Walker, JA. Todd, D. Easton, DG. Clayton, PR. Burton, MD. Tobin, JC. Barrett, DM. Evans, AP. Morris, LR. Cardon, NJ. Cardin, D. Davison, T. Ferreira, J. Pereira-Gale, IB. Hallgrimsdóttir, BN. Bowie, JL. Marchini, CC. Spencer, Z. Su, YY. Teo, D. Vukcevic, P. Donnelly, D. Bentley, MA. Brown, LR. Cardon, M. Caulfield, DG. Clayton, A. Compston, N. Craddock, P. Deloukas, P. Donnelly, M. Farrall, SC. Gough, AS. Hall, AT. Hattersley, AV. Hill, DP. Kwiatkowski, CG. Mathew, MI. McCarthy, WH. Ouwehand, M. Parkes, M. Pembrey, N. Rahman, NJ. Samani, MR. Stratton, JA. Todd, J. Worthington, S. Kathiresan, JB. Meigs, G. Williams, DM. Nathan, CA. MacRae, CJ. O'Donnell, D. Ardissino, PA. Merlini, C. Berzuini, L. Bernardinelli, F. Peyvandi, M. Tubaro, P. Celli, M. Ferrario, R. Fetiveau, N. Marziliano, G. Casari, M. Galli, F. Ribichini, M. Rossi, F. Bernardi, P. Zonzin, A. Piazza, PM. Mannucci, SM. Schwartz, DS. Siscovick, J. Yee, Y. Friedlander, R. Elosua, J. Marrugat, G. Lucas, I. Subirana, J. Sala, R. Ramos, V. Salomaa, AS. Havulinna, L. Peltonen, O. Melander, G. Berglund, BF. Voight, S. Kathiresan, JN. Hirschhorn, R. Asselta, S. Duga, M. Spreafico, K. Musunuru, MJ. Daly, S. Purcell, SM. Schwartz, J. Yee, S. Kathiresan, G. Lucas, I. Subirana, R. Elosua, A. Surti, C. Guiducci, L. Gianniny, D. Mirel, M. Parkin, N. Burtt, SB. Gabriel. - In: THE LANCET. - ISSN 0140-6736. - 377:9763(2011 Jan 29), pp. 383-392. [10.1016/S0140-6736(10)61996-4]
			
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						M.P. Reilly, M. Li, J. He, J.F. Ferguson, I.M. Stylianou, N.N. Mehta, M.S. Burnett, J.M. Devaney, C.W. Knouff, J.R. Thompson, B.D. Horne, A.F. Stewart...espandi
						
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