A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3087560 90 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size. © 2015 Nature America, Inc.
Έτος δημοσίευσης:
2015
Συγγραφείς:
Nikpay, M.
Goel, A.
Won, H.-H.
Hall, L.M.
Willenborg, C.
Kanoni, S.
Saleheen, D.
Kyriakou, T.
Nelson, C.P.
CHopewell, J.
Webb, T.R.
Zeng, L.
Dehghan, A.
Alver, M.
MArmasu, S.
Auro, K.
Bjonnes, A.
Chasman, D.I.
Chen, S.
Ford, I.
Franceschini, N.
Gieger, C.
Grace, C.
Gustafsson, S.
Huang, J.
Hwang, S.-J.
Kim, Y.K.
Kleber, M.E.
Lau, K.W.
Lu, X.
Lu, Y.
Lyytikäinen, L.-P.
Mihailov, E.
Morrison, A.C.
Pervjakova, N.
Qu, L.
Rose, L.M.
Salfati, E.
Saxena, R.
Scholz, M.
Smith, A.V.
Tikkanen, E.
Uitterlinden, A.
Yang, X.
Zhang, W.
Zhao, W.
De Andrade, M.
De Vries, P.S.
Van Zuydam, N.R.
Anand, S.S.
Bertram, L.
Beutner, F.
Dedoussis, G.
Frossard, P.
Gauguier, D.
Goodall, A.H.
Gottesman, O.
Haber, M.
Han, B.-G.
Huang, J.
Jalilzadeh, S.
Kessler, T.
König, I.R.
Lannfelt, L.
Lieb, W.
Lind, L.
MLindgren, C.
Lokki, M.-L.
Magnusson, P.K.
Mallick, N.H.
Mehra, N.
Meitinger, T.
Memon, F.-U.-R.
Morris, A.P.
Nieminen, M.S.
Pedersen, N.L.
Peters, A.
Rallidis, L.S.
Rasheed, A.
Samuel, M.
Shah, S.H.
Sinisalo, J.
EStirrups, K.
Trompet, S.
Wang, L.
Zaman, K.S.
Ardissino, D.
Boerwinkle, E.
Borecki, I.B.
Bottinger, E.P.
Buring, J.E.
Chambers, J.C.
Collins, R.
Cupples, L.
Danesh, J.
Demuth, I.
Elosua, R.
Epstein, S.E.
Esko, T.
Feitosa, M.F.
Franco, O.H.
Franzosi, M.G.
Granger, C.B.
Gu, D.
Gudnason, V.
SHall, A.
Hamsten, A.
Harris, T.B.
LHazen, S.
Hengstenberg, C.
Hofman, A.
Ingelsson, E.
Iribarren, C.
Jukema, J.W.
Karhunen, P.J.
Kim, B.-J.
Kooner, J.S.
Kullo, I.J.
Lehtimäki, T.
Loos, R.J.F.
Melander, O.
Metspalu, A.
März, W.
Palmer, C.N.
Perola, M.
Quertermous, T.
Rader, D.J.
Ridker, P.M.
Ripatti, S.
Roberts, R.
Salomaa, V.
Sanghera, D.K.
Schwartz, S.M.
Seedorf, U.
Stewart, A.F.
Stott, D.J.
Thiery, J.
Zalloua, P.A.
O'Donnell, C.J.
Reilly, M.P.
Assimes, T.L.
Thompson, J.R.
Erdmann, J.
Clarke, R.
Watkins, H.
Kathiresan, S.
McPherson, R.
Deloukas, P.
Schunkert, H.
Samani, N.J.
Farrall, M.
Περιοδικό:
Nature Genetics
Εκδότης:
Nature Publishing Group
Τόμος:
47
Αριθμός / τεύχος:
10
Σελίδες:
1121-1130
Λέξεις-κλειδιά:
acute coronary syndrome; Article; controlled study; coronary artery disease; coronary artery obstruction; genetic association; genetic model; genetic susceptibility; genetic variability; heart infarction; heritability; human; human genome; major clinical study; phenotype; priority journal; quantitative trait locus; risk factor; single nucleotide polymorphism; stable angina pectoris; coronary artery disease; genetics; genome-wide association study; human genome; meta analysis, Coronary Artery Disease; Genome, Human; Genome-Wide Association Study; Humans; Phenotype
Επίσημο URL (Εκδότης):
DOI:
10.1038/ng.3396
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