Large-scale gene-centric analysis identifies novel variants for coronary artery disease
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Publication date
2011-09-01
Authors
Butterworth, Adam S.
Braund, Peter
Farrall, Martin
Hardwick, Robert J.
Saleheen, Danish
Peden, John
Soranzo, Nicole
Chambers, John C.
Sivapalaratnam, Suthesh
Kleber, Marcus E.
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Article
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Abstract
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ~2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p
Keywords
lipid, ABCG5 gene, ABCG8 gene, adult, article, Asian, cardiovascular risk, case control study, chromosome 9p, COL4A1 gene, COL4A2 gene, controlled study, coronary artery disease, CYP17A1 gene, Europe, female, gene, gene expression, gene frequency, genetic analysis, genetic association, genetic predisposition, genetic variability, human, IL5 gene, large scale gene centric analysis, LIPA gene, major clinical study, male, race difference, risk assessment, risk factor, TRIB1 gene, ZC3HC1 gene, SDG 3 - Good Health and Well-being
Citation
Butterworth, A S, Braund, P, Farrall, M, Hardwick, R J, Saleheen, D, Peden, J, Soranzo, N, Chambers, J C, Sivapalaratnam, S, Kleber, M E, Keating, B, Qasim, A, Klopp, N, Erdmann, J, Assimes, T L, Ball, S G, Balmforth, A J, Barnes, T, Basart, H, Baumert, J, Bezzina, C R, Boerwinkle, E, Boehm, B O, Brocheton, J, Bugert, P, Cambien, F, Clarke, R, Codd, V, Collins, R, Couper, D, Adrienne Cupples, L, de Jong, J S, Diemert, P, Ejebe, K, Elbers, C C, Elliott, P, Fornage, M, Franzosi, M-G, Frossard, P, Garner, S, Goel, A, Goodall, A H, Hengstenberg, C, Hunt, S E, Kastelein, J J P, Klungel, O H, Klüterr, H, Koch, K T, König, I R, Kooner, A S, Laaksonen, R, Lathrop, M, Li, M, Liu, K, McPherson, R, Musameh, M D, Musani, S, Nelson, C P, O'Donnell, C J, Ongen, H, Papanicolaou, G, Peters, A, Peters, B J M, Potter, S, Psaty, B M, Qu, L, Rader, D J, Rasheed, A, Rice, C, Scott, J, Seedorf, U, Sehmi, J S, Sotoodehnia, N, Stark, K, Stephens, J, van der Schoot, C E, van der Schouw, Y T, Thorsteinsdottir, U, Tomaszewski, M, van der Harst, P, Vasan, R S, Wilde, A A M, Willenborg, C, Winkelmann, B R, Zaidi, M, Zhang, W, Ziegler, A, de Bakker, P I W, Koenig, W, März, W, Trip, M D, Reilly, M, Kathiresan, S, Schunkert, H, Hamsten, A, Hall, A S, Kooner, J S, Thompson, S G, Thompson, J R, Deloukas, P, Ouwehand, W H, Watkins, H, Danesh, J, Samani, N J, Rafelt, S, Bruinsma, N, Dekker, L R, Henriques, J P, de Winter, R J, Alings, M, Allaart, C F, Gorgels, A P, Verheugt, F W, Mueller, M, Meisinger, C, DerOhannessian, S, Mehta, N N, Ferguson, J, Hakonarson, H, Matthai, W, Wilensky, R, Hopewell, J C, Parish, S, Linksted, P, Notman, J, Gonzalez, H, Young, A, Ostley, T, Munday, A, Goodwin, N, Verdon, V, Shah, S, Cobb, L, Edwards, C, Mathews, C, Gunter, R, Benham, J, Davies, C, Cobb, M, Crowther, J, Richards, A, Silver, M, Tochlin, S, Mozley, S, Clark, S, Radley, M, Kourellias, K, Olsson, P, Barlera, S, Tognoni, G, Rust, S, Assmann, G, Heath, S, Zelenika, D, Gut, I, Green, F, Aly, A, Anner, K, Björklund, K, Blomgren, G, Cederschiöld, B, Danell-Toverud, K, Eriksson, P, Grundstedt, U, Heinonen, M, Hellénius, M-L, van't Hooft, F, Husman, K, Lagercrantz, J, Larsson, A, Larsson, M, Mossfeldt, M, Mälarstig, A, Olsson, G, Sabater-Lleal, M, Sennblad, B, Silveira, A, Strawbridge, R, Söderholm, B, Öhrvik, J, Shah Zaman, K, Hayat Mallick, N, Azhar, M, Samad, A, Ishaq, M, Shah, N, Samuel, M, Holm, H, Preuss, M, Stewart, A F R, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, S, Andersen, K, Anderson, J L, Ardissino, D, Becker, L C, Becker, D M, Berger, K, Bis, J C, Matthijs Boekholdt, S, Brown, M J, Susan Burnett, M, Buysschaert, I, Carlquist, J F, Chen, L, Davies, R W, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, J, Do, R, Doering, A, El Mokhtari, N E, Ellis, S G, Elosua, R, Engert, J C, Epstein, S, de Faire, U, Fischer, M, Folsom, A R, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, J R, Tennstedt, S, Halperin, E, Hammond, N, Hazen, S L, Hofman, A, Horne, B D, Illig, T, Iribarren, C, Jones, G T, Wouter Jukema, J, Kaiser, M A, Kaplan, L M, Khaw, K-T, Knowles, J W, Kolovou, G, Kong, A, Lambrechts, D, Leander, K, Lieb, W, Lettre, G, Loley, C, Lotery, A J, Mannucci, P M, Maouche, S, Martinelli, N, McKeown, P P, Meitinger, T, Melander, O, Angelica Merlini, P, Mooser, V, Morgan, T, Mühleisen, T W, Muhlestein, J B, Musunuru, K, Nahrstaedt, J, Nöthen, M M, Olivieri, O, Peyvandi, F, Patel, R S, Patterson, C C, Quyyumi, A A, Rallidis, L S, Roosendaal, F R, Rubin, D, Salomaa, V, Lourdes Sampietro, M, Sandhu, M S, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, S M, Siscovick, D S, Sivananthan, M, Smith, A V, Smith, T B, Snoep, J D, Spertus, J A, Stefansson, K, Stirrups, K, Stoll, M, Wilson Tang, W H, Thorgeirsson, G, Thorleifsson, G, Uitterlinden, A G, van Rij, A M, Voight, B F, Wareham, N J, Wells, G A, Wichmann, H -E, Witteman, J C M, Wright, B J, Ye, S, Quertermous, T, Blankenberg, S, Roberts, R, Onland-Moret, N C, van Setten, J, Monique Verschuren, W M, Boer, J M A, Wijmenga, C, Hofker, M H, Maitland-van der Zee, A-H, de Boer, A, Grobbee, D E, Attwood, T, Belz, S, Cooper, J, Crisp-Hihn, A, Foad, N, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd-Jones, H, Lugauer, I, Lundmark, P, Moore, J S, Muir, D, Murray, E, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Rankin, A, Rice, C M, Sager, H, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Syvannen, A-C & Wallace, C 2011, 'Large-scale gene-centric analysis identifies novel variants for coronary artery disease', PLoS Genetics, vol. 7, no. 9. https://doi.org/10.1371/journal.pgen.1002260