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

Henning Jansen; Christina Willenborg; Sabrina Schlesinger; Paola G. Ferrario; Inke R. König; Jeanette Erdmann; Nilesh J. Samani; Wolfgang Lieb; Heribert Schunkert

doi:10.1007/s00438-015-1045-3

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

Henning Jansen^*, Christina Willenborg, Sabrina Schlesinger, Paola G. Ferrario, Inke R. König, Jeanette Erdmann, Nilesh J. Samani, Wolfgang Lieb, Heribert Schunkert

^*Corresponding author for this work

7 Citations (Scopus)

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.

Original language	English
Journal	Molecular Genetics and Genomics
Volume	290
Issue number	5
Pages (from-to)	1911-1917
Number of pages	7
ISSN	1617-4615
DOIs	https://doi.org/10.1007/s00438-015-1045-3
Publication status	Published - 23.10.2015

Funding

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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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 5 Gender Equality

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Research Area: Medical Genetics

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10.1007/s00438-015-1045-3

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title = "Genetic variants associated with celiac disease and the risk for coronary artery disease",

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.",

author = "Henning Jansen and Christina Willenborg and Sabrina Schlesinger and Ferrario, \{Paola G.\} and K{\"o}nig, \{Inke R.\} and Jeanette Erdmann and Samani, \{Nilesh J.\} and Wolfgang Lieb and Heribert Schunkert",

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T1 - Genetic variants associated with celiac disease and the risk for coronary artery disease

AU - Jansen, Henning

AU - Willenborg, Christina

AU - Schlesinger, Sabrina

AU - Ferrario, Paola G.

AU - König, Inke R.

AU - Erdmann, Jeanette

AU - Samani, Nilesh J.

AU - Lieb, Wolfgang

AU - Schunkert, Heribert

PY - 2015/10/23

Y1 - 2015/10/23

N2 - 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.

AB - 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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DO - 10.1007/s00438-015-1045-3

M3 - Journal articles

C2 - 25893417

AN - SCOPUS:84941996291

SN - 1617-4615

VL - 290

SP - 1911

EP - 1917

JO - Molecular Genetics and Genomics

JF - Molecular Genetics and Genomics

IS - 5

ER -

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

Abstract

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