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Genetic variants associated with celiac disease and the risk for coronary artery disease

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Abstract

Epidemiological evidence suggests that patients with celiac disease are at increased risk for coronary artery disease (CAD). Genetic-epidemiological analyses identified many single nucleotide polymorphisms (SNPs) associated with celiac disease. If there is a causal relation between celiac disease and CAD, one might expect that risk alleles primarily associated with celiac disease also increase the risk of CAD. In this study we identified from literature 41 SNPs that have been previously described to be genome-wide associated with celiac disease (p < 5 × 10−08). These SNPs were evaluated for their association with CAD in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) dataset, a meta-analysis comprising genome-wide SNP association data from 22,233 CAD cases and 64,762 controls. 24 out of 41 (58.5 %) risk alleles for celiac disease displayed a positive association with CAD (CAD-OR range 1.001–1.081). The remaining risk alleles for celiac disease (n = 16) revealed CAD-ORs of ≤1.0 (range 0.951–1.0). The proportion of CAD associated alleles was greater but did not differ significantly from the proportion of 50 % expected by chance (p = 0.069). One SNP (rs653178 at the SH2B3/ATXN2 locus) displayed study-wise statistically significant association with CAD with directionality consistent effects on celiac disease and CAD. However, the effect of this locus is most likely driven by pleiotropic effects on multiple other diseases. In conclusion, this genetically based approach provided no convincing evidence that SNPs associated with celiac disease contribute to the risk of CAD. Hence, common non-genetic factors may play a more important role explaining the coincidence of these two complex disease conditions.

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Acknowledgments

This work was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (Grant# 01ZX1306). Furthermore, this project was supported by the EU-funded Integrated Projects Cardiogenics (LSHM-CT-2006-037593), CVgenes@target and ENGAGE as well as the BMBF-funded German National Genome Network (NGFN-Plus) Project Atherogenomics (FKZ: 01GS0831) and e:AtheroSysMed, with participation in the German Excellence Center of Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance. WL has in part been supported by the BMBF-funded (federal ministry for education and research) project GANI_MED (03IS2061A). Information regarding the CARDIoGRAM members, acknowledgements, funding sources and disclosures are detailed in the online supplement.

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    Authors and Affiliations

    1. Deutsches Herzzentrum München and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Technische Universität München, Lazarettstr. 36, 80636, Munich, Germany

      Henning Jansen & Heribert Schunkert

    2. Institut für integrative und experimentelle Genomik, DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Universität zu Lübeck, Lübeck, Germany

      Christina Willenborg & Jeanette Erdmann

    3. Institut für Epidemiologie, Christian-Albrechts Universität zu Kiel, Kiel, Germany

      Sabrina Schlesinger & Wolfgang Lieb

    4. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany

      Paola G. Ferrario & Inke R. König

    5. Department of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9QP, UK

      Nilesh J. Samani

    6. Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, LE3 9QP, UK

      Nilesh J. Samani

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    1. Henning Jansen
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    2. Christina Willenborg
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    Correspondence to Henning Jansen.

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    Communicated by S. Hohmann.

    On behalf of CARDIoGRAM.

    H. Jansen and C. Willenborg contributed equally.

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    Jansen, H., Willenborg, C., Schlesinger, S. et al. Genetic variants associated with celiac disease and the risk for coronary artery disease. Mol Genet Genomics 290, 1911–1917 (2015). https://doi.org/10.1007/s00438-015-1045-3

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    • DOI: https://doi.org/10.1007/s00438-015-1045-3

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