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Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease


We identify the SLC22A3-LPAL2-LPA gene cluster as a strong susceptibility locus for coronary artery disease (CAD) through a genome-wide haplotype association (GWHA) study. This locus was not identified from previous genome-wide association (GWA) studies focused on univariate analyses of SNPs. The proposed approach may have wide utility for analyzing GWA data for other complex traits.

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Figure 1: Haplotypic odds ratios (ORs) for CAD associated with the CCTC and CTTG haplotypes derived from rs2048327, rs3127599, rs7767084 and rs10755578 on chromosome 6q26–q27.


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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 German Study was supported by the Deutsche Forschungsgemeinschaft, the German Federal Ministry of Education and Research in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus). 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. This work has also been partially supported by the EGEE-II project funded by the European Union INFSO-RI-031688. N.J.S. is supported by a Chair funded by the BHF. The main sponsor of the current analysis is the EU funded integrated project 'Cardiogenics' (LSHM-CT-2006-037593).

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This work was designed by D.-A.T., L.T., F.C., H.S. and N.J.S. Statistical analyses were carried out by D.-A.T., I.R.K., A.G., M.P., P.H., A.Z. and J.R.T., J.E., P.S.B., C.P., M.D., P.B. and W.O. supervised and/or participated in the genetic laboratory analyses. A.M. developed the computing grid program under the supervision of D.-A.T. and C.G. Case collections were coordinated by P.S.B., A.S.H., B.J.W., A.J.B., S.G.B., W.O., J.R.T., N.J.S. (WTCCC), J.E., T.M., H.-E.W., C. Meisinger, C.H., K.N., K.S., J.S., D.R. (GerMIFS), S.S., A.S., N.E.E.-M. (PopGene), J.E., P.L.-N. (Angio-Luebeck), A.E., D.A., G.L., J.-B.R., and C. Morrison (ECTIM). D.A.T., L.T., F.C., H.S. and N.J.S. drafted the manuscript with substantial contributions from I.R.K., J.E., A.Z.

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Correspondence to David-Alexandre Trégouët.

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

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Supplementary Methods, Supplementary Tables 1–3, Supplementary Figures 1–3 and Supplementary Note (PDF 746 kb)

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Trégouët, DA., König, I., Erdmann, J. et al. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat Genet 41, 283–285 (2009).

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