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Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes
BACKGROUND: Patients with type 1 diabetes are more at risk of coronary artery disease than the general population. Although evidence points to a genetic risk there have been no study investigating genetic risk factors of coronary artery disease specific to individuals with type 1 diabetes. To identi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916834/ https://www.ncbi.nlm.nih.gov/pubmed/29695241 http://dx.doi.org/10.1186/s12933-018-0705-0 |
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author | Charmet, Romain Duffy, Seamus Keshavarzi, Sareh Gyorgy, Beata Marre, Michel Rossing, Peter McKnight, Amy Jayne Maxwell, Alexander P. Ahluwalia, Tarun veer Singh Paterson, Andrew D. Trégouët, David-Alexandre Hadjadj, Samy |
author_facet | Charmet, Romain Duffy, Seamus Keshavarzi, Sareh Gyorgy, Beata Marre, Michel Rossing, Peter McKnight, Amy Jayne Maxwell, Alexander P. Ahluwalia, Tarun veer Singh Paterson, Andrew D. Trégouët, David-Alexandre Hadjadj, Samy |
author_sort | Charmet, Romain |
collection | PubMed |
description | BACKGROUND: Patients with type 1 diabetes are more at risk of coronary artery disease than the general population. Although evidence points to a genetic risk there have been no study investigating genetic risk factors of coronary artery disease specific to individuals with type 1 diabetes. To identify low frequency and common genetic variations associated with coronary artery disease in populations of individuals with type 1 diabetes. METHODS: A two-stage genome wide association study was conducted. The discovery phase involved the meta-analysis of three genome-wide association cohorts totaling 434 patients with type 1 diabetes and coronary artery disease (cases) and 3123 T1D individuals with no evidence of coronary artery disease (controls). Replication of the top association signals (p < 10(−5)) was performed in five additional independent cohorts totaling 585 cases and 2612 controls. RESULTS: One locus (rs115829748, located upstream of the MAP1B gene) reached the statistical threshold of 5 × 10(−8) for genome-wide significance but did not replicate. Nevertheless, three single nucleotide polymorphisms provided suggestive evidence for association with coronary artery disease in the combined studies: CDK18 rs138760780 (OR = 2.60 95% confidence interval [1.75–3.85], p = 2.02 × 10(−6)), FAM189A2 rs12344245 (OR = 1.85 [1.41–2.43], p = 8.52 × 10(−6)) and PKD1 rs116092985 (OR = 1.53 [1.27–1.85], p = 1.01 × 10(−5)). In addition, our analyses suggested that genetic variations at the ANKS1A, COL4A2 and APOE loci previously found associated with coronary artery disease in the general population could have stronger effects in patients with type 1 diabetes. CONCLUSIONS: This study suggests three novel candidate genes for coronary artery disease in the subgroup of patients affected with type 1 diabetes. The detected associations deserve to be definitively validated in additional epidemiological studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-018-0705-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5916834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59168342018-04-30 Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes Charmet, Romain Duffy, Seamus Keshavarzi, Sareh Gyorgy, Beata Marre, Michel Rossing, Peter McKnight, Amy Jayne Maxwell, Alexander P. Ahluwalia, Tarun veer Singh Paterson, Andrew D. Trégouët, David-Alexandre Hadjadj, Samy Cardiovasc Diabetol Original Investigation BACKGROUND: Patients with type 1 diabetes are more at risk of coronary artery disease than the general population. Although evidence points to a genetic risk there have been no study investigating genetic risk factors of coronary artery disease specific to individuals with type 1 diabetes. To identify low frequency and common genetic variations associated with coronary artery disease in populations of individuals with type 1 diabetes. METHODS: A two-stage genome wide association study was conducted. The discovery phase involved the meta-analysis of three genome-wide association cohorts totaling 434 patients with type 1 diabetes and coronary artery disease (cases) and 3123 T1D individuals with no evidence of coronary artery disease (controls). Replication of the top association signals (p < 10(−5)) was performed in five additional independent cohorts totaling 585 cases and 2612 controls. RESULTS: One locus (rs115829748, located upstream of the MAP1B gene) reached the statistical threshold of 5 × 10(−8) for genome-wide significance but did not replicate. Nevertheless, three single nucleotide polymorphisms provided suggestive evidence for association with coronary artery disease in the combined studies: CDK18 rs138760780 (OR = 2.60 95% confidence interval [1.75–3.85], p = 2.02 × 10(−6)), FAM189A2 rs12344245 (OR = 1.85 [1.41–2.43], p = 8.52 × 10(−6)) and PKD1 rs116092985 (OR = 1.53 [1.27–1.85], p = 1.01 × 10(−5)). In addition, our analyses suggested that genetic variations at the ANKS1A, COL4A2 and APOE loci previously found associated with coronary artery disease in the general population could have stronger effects in patients with type 1 diabetes. CONCLUSIONS: This study suggests three novel candidate genes for coronary artery disease in the subgroup of patients affected with type 1 diabetes. The detected associations deserve to be definitively validated in additional epidemiological studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12933-018-0705-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-25 /pmc/articles/PMC5916834/ /pubmed/29695241 http://dx.doi.org/10.1186/s12933-018-0705-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Investigation Charmet, Romain Duffy, Seamus Keshavarzi, Sareh Gyorgy, Beata Marre, Michel Rossing, Peter McKnight, Amy Jayne Maxwell, Alexander P. Ahluwalia, Tarun veer Singh Paterson, Andrew D. Trégouët, David-Alexandre Hadjadj, Samy Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
title | Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
title_full | Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
title_fullStr | Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
title_full_unstemmed | Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
title_short | Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
title_sort | novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916834/ https://www.ncbi.nlm.nih.gov/pubmed/29695241 http://dx.doi.org/10.1186/s12933-018-0705-0 |
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