Abstract
Coronary artery disease (CAD) causes more than 700,000 deaths each year in China. Previous genome-wide association studies (GWAS) in populations of European ancestry identified several genetic loci for CAD, but no such study has yet been reported in the Chinese population. Here we report a three-stage GWAS in the Chinese Han population. We identified a new association between rs6903956 in a putative gene denoted as C6orf105 on chromosome 6p24.1 and CAD (P = 5.00 × 10−3, stage 2 validation; P = 3.00 × 10−3, P = 1.19 × 10−8 and P = 4.00 × 10−3 in three independent stage 3 replication populations; P = 4.87 × 10−12, odds ratio = 1.51 in the combined population). The minor risk allele A of rs6903956 is associated with decreased C6orf105 mRNA expression. We report the first GWAS for CAD in the Chinese Han population and identify a SNP, rs6903956, in C6orf105 associated with susceptibility to CAD in this population.
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Acknowledgements
We thank the study subjects for their participation in and support of this project. We greatly appreciate the generous help from L. Li, G.Q. Shen, Y.J. Qian, F. Xu, F.C. Sun, F.S. Ji, B. Liu, X.Y. Zhou, Y. Xiao, S. Rao and B. Yang. This study was supported by China National 863 Scientific Program (2006AA02Z476), the China National Basic Research Program (973 program 2007CB512002), a Hubei Province Natural Science Key Program (2008CDA047), a Key Academic Program Leader Award of Wuhan City (200951830560), the National Natural Science Foundation of China (30670857, 30800457 and 81070106) and in part by the Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic.
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Contributions
Study concept and design: Q.K.W., J.-P.C., X.T., Q.H. and M.-G.L.
Acquisition of data: C.-Q.X., Q.H., J.-P.C., X.-C.L., D.W., X.X., Y.-H.L., Q.-T.Z., X.C., Y.-Z.Y., C.L., R.Y., C.-C.W., G.W., Q.-L.L., Y.B., Y.-F.H., D.Y., Q.Y., X.-J.W., D.-P.D., R.-F.Z., J.W., J.-H.R., S.-S.L., Y.-Y.Z., F.-F.F., Y.H., Q.-X.L., S.-W.S., N.L., Z.-W.P., Y.L., B.Y., Y.-X.W., Y.-H.K., J.L., N.W., C.-Y.L., L.-Y.J., L.-J.G., L.L., H. Liu, E.-W.H., J.C., N.J., X.R., H. Li, T.K., X.-Q.Z., J.-Y.L., H.X., B.Y., L.-S.S. and Y.-L.X.
Analysis and interpretation of data: C.-Q.X., F.W., D.-P.D., J.-P.C., L.-S.S., X.-C.L., D.W., X.X., Q.H., X.T. and Q.K.W.
Drafting of the manuscript: C.-Q.X., F.W. and X.T.
Critical revision of the manuscript: Q.K.W., F.W. and C.-Q.X.
Statistical analysis: F.W. and C.-Q.X.
Study supervision: Q.K.W., Q.H., J.-P.C., X.T., Y.-H.L. and Y.-Z.Y.
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Wang, F., Xu, CQ., He, Q. et al. Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nat Genet 43, 345–349 (2011). https://doi.org/10.1038/ng.783
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DOI: https://doi.org/10.1038/ng.783
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