Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Nelson, CP; Goel, A; Butterworth, AS; Kanoni, S; Webb, TR; Marouli, E; Zeng, L; Ntalla, I; Lai, FY; Hopewell, JC; Giannakopoulou, O; Jiang, T; Hamby, SE; Di Angelantonio, E; Assimes, TL; Bottinger, EP; Chambers, JC; Clarke, R; Palmer, CNA; Cubbon, RM; Ellinor, P; Ermel, R; Evangelou, E; Franks, PW; Grace, C; Gu, D; Hingorani, AD; Howson, JMM; Ingelsson, E; Kastrati, A; Kessler, T; Kyriakou, T; Lehtimäki, T; Lu, X; Lu, Y; März, W; McPherson, R; Metspalu, A; Pujades-Rodriguez, M; Ruusalepp, A; Schadt, EE; Schmidt, AF; Sweeting, MJ; Zalloua, PA; AlGhalayini, K; Keavney, BD; Kooner, JS; Loos, RJF; Patel, RS; Rutter, MK; Tomaszewski, M; Tzoulaki, I; Zeggini, E; Erdmann, J; Dedoussis, G; Björkegren, JLM; EPIC-CVD Consortium; CARDIoGRAMplusC4D; UK Biobank CardioMetabolic Consortium CHD working group; Schunkert, H; Farrall, M; Danesh, J; Samani, NJ; Watkins, H; Deloukas, P.
Association analyses based on false discovery rate implicate new loci for coronary artery disease.
Nat Genet. 2017; 49(9):1385-1391 Doi: 10.1038/ng.3913 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz: März Winfried
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Abstract:: Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10^-8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n_cases = 10,801) as well as a stricter definition without angina (HARD; n_cases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
Find related publications in this database (using NLM MeSH Indexing): Coronary Artery Disease - genetics; Genetic Association Studies - methods; Genetic Association Studies - standards; Genetic Association Studies - statistics & numerical data; Genetic Loci - genetics; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study - methods; Genome-Wide Association Study - standards; Genome-Wide Association Study - statistics & numerical data; Genotype -; Health Information Systems - standards; Health Information Systems - statistics & numerical data; Humans -; Meta-Analysis as Topic -; Phenotype -; Polymorphism, Single Nucleotide -; Reproducibility of Results -; Risk Factors -; United Kingdom -