New susceptibility locus for coronary artery disease on chromosome 3q22.3

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Abstract

We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 × 10−13; OR = 1.15, 95% CI = 1.11–1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 × 10−7; OR = 1.08, 95% CI = 1.05–1.11).

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Figure 1: Association results from Stage 1.

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Acknowledgements

We thank J. Stegmann, A. Medack, S. Wrobel and A. Thiemig for assistance. We thank M. Scholz and J. Neudert (Trium Analysis Online GmbH, Munich, Germany) for database management. The German Study was supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus). The WTCCC Study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC Study was carried out by the British Heart Foundation (BHF) Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. We also acknowledge support of the Wellcome Trust Functional Genomics Initiative in Cardiovascular Genetics. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the GSF-National Research centre for Environment and Health, which is funded by the German Federal Ministry of Education and Research and of the State of Bavaria. N.J.S. and S.G.B. are supported by Chairs funded by the BHF. Recruitment for the Italian Atherosclerosis, Thrombosis and Vascular Biology Working Group was supported by the “Associazione per lo Studio della Trombosi in Cardiologia.” The MIGen/IATVB genotyping was supported by a grant to D. Altshuler (R01HL087676) from the STAMPEED program of the National Heart, Lung, and Blood Institute, US National Institutes of Health. In addition, the MIGen study was supported by grants from the Fannie Rippel Foundation (to S.K.) and the Doris Duke Charitable Foundation (to S.K.). The Broad Institute Center for Genotyping and Analysis subsidized genotyping in the MIGen study with support from the National Center for Research Resources (U54RR020278). The main sponsor of the current analysis is the EU-funded integrated project Cardiogenics (LSHM-CT-2006-037593).

Author information

The study was designed by H.S., N.J.S., A.Z., I.R.K., J.R.T. and J.E. Subject ascertainment, recruitment and medical record review was organized and carried out by C.H., P.L.-N. and M.F. DNA material collection, handling and genotyping (Affymetrix 500K, 6.0, and TaqMan) was supervised by P.D., T.M., P. Bruse, W.H.O., P.S.B., K.S., C.P. and A. Schäfer Statistical analysis was carried out by A.G., D.F.S., I.R.K., B.W., A. Schillert, D.-A.T., J.R.T. and A.Z. RT-PCRs were carried out by Z.A. and A.K.W., J.E., N.J.S and H.S. drafted the manuscript with substantial contributions from I.R.K, A.G. and A.Z. Principal collaborators for the case cohorts were W.M. and W.R. (LURIC), H.K. and P. Bugert (GerBS), P.L.-N. (Angio-Luebeck), N.E.M., S.S., J.S. and D.R. (PopGen), H.-E.W., T.M., C.M., A.P., and J.B. (KORA), N.J.S., A.S.H., S.G.B., P.S.B. and A.J.B. (UKMI), C.H., M.F., K.S. (GO-KARD), S.K., D. Altshuler, B.F.V., D. Ardissino, O.M., C.J.O´D., R.E., V.S., L.P., D.S.S. and S.M.S. (MIGen), P.A.M., F.P., L.B. and D. Ardissino (IATVB), S.B., T.Z. and P.W. (Atherogene), L.T., C.P. and F.C. (ECTIM). All authors contributed to the final version of the manuscript.

Correspondence to Jeanette Erdmann.

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A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

Supplementary information

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Supplementary Methods, Supplementary Figures 1–5, Supplementary Tables 1–4 and Supplementary Note (PDF 1382 kb)

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