TY - JOUR
T1 - Association analyses based on false discovery rate implicate many new loci for coronary artery disease
AU - Nelson, Christopher P
AU - Goel, Anuj
AU - Butterworth, Adam S
AU - Kanoni, Stavroula
AU - Webb, Tom R.
AU - Marouli, Eirini
AU - Zeng, Lingyao
AU - Ntalla, Ioanna
AU - Lai, Florence Y
AU - Hopewell, Jemma C
AU - Giannakopoulou, Olga
AU - Jiang, Tao
AU - Hamby, Stephen E.
AU - Di Angelantonio, Emanuele
AU - Assimes, Themistocles L.
AU - Bottinger, Erwin P.
AU - Chambers, John C.
AU - Clarke, Robert
AU - Palmer, Colin NA
AU - Cubbon, Richard M.
AU - Ellinor, Patrick
AU - Ermel, Raili
AU - Evangelou, Evangelos
AU - Franks, Paul W.
AU - Grace, Christopher
AU - Gu, Dongfeng
AU - Hingorani, Aroon D.
AU - Howson, Joanna M.M.
AU - Ingelsson, Erik
AU - Kastrati, Adnan
AU - Kessler, Thorsten
AU - Kyriakou, Theodosios
AU - Lehtimäki, Terho
AU - Lu, Xiangfeng
AU - Lu, Yingchang
AU - Maerz, Winfried
AU - McPherson, Ruth
AU - Metspalu, Andres
AU - Pujades-Rodriguez, Mar
AU - Ruusalepp, Arno
AU - Schadt, Eric E.
AU - Schmidt, Amand F.
AU - Sweeting, Michael J.
AU - Zalloua, Pierre A
AU - AIGhalayini, Kamal
AU - Keavney, Bernard
AU - Kooner, Jaspal S.
AU - Loos, Ruth J F
AU - Rutter, Martin
AU - Tomaszewski, Maciej
AU - EPIC-CVD Consortium
AU - CARDIoGRAMplusC4D
AU - The UK Biobank CardioMetabolic Consortium CHD working group
PY - 2017/7/17
Y1 - 2017/7/17
N2 - Genome-wide association studies (GWAS) in coronary artery disease (CAD) have identified 66 loci at ‘genome-wide significance’ (p < 5 × 10-8) but a much larger number of putative loci at a false discovery rate (FDR) of 5%1-4. 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; Ncases=10,801) as well as a stricter definition without it (HARD; Ncases=6,482) and selected the former for conducting a meta-analysis with the two most recent CAD GWASs2-3. This approach identified 13 new loci at genome-wide significance, 12 of which were in our previous 5% FDR list2, and provided strong support that the remaining FDR loci represent genuine signals. The set of 304 independent variants at 5% FDR in this study explain 21.2% of CAD heritability and identified 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
AB - Genome-wide association studies (GWAS) in coronary artery disease (CAD) have identified 66 loci at ‘genome-wide significance’ (p < 5 × 10-8) but a much larger number of putative loci at a false discovery rate (FDR) of 5%1-4. 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; Ncases=10,801) as well as a stricter definition without it (HARD; Ncases=6,482) and selected the former for conducting a meta-analysis with the two most recent CAD GWASs2-3. This approach identified 13 new loci at genome-wide significance, 12 of which were in our previous 5% FDR list2, and provided strong support that the remaining FDR loci represent genuine signals. The set of 304 independent variants at 5% FDR in this study explain 21.2% of CAD heritability and identified 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
UR - https://www.scopus.com/pages/publications/85028693072
U2 - 10.1038/ng.3913
DO - 10.1038/ng.3913
M3 - Article
SN - 1061-4036
VL - 49
SP - 1385
EP - 1391
JO - Nature Genetics
JF - Nature Genetics
ER -
