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Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes

Type 2 diabetes (T2D) is an important heritable risk factor for coronary artery disease (CAD), the risk of both diseases being increased by metabolic syndrome (MS). With the availability of large‐scale genome‐wide association data, we aimed to elucidate the genetic burden of CAD risk in T2D predispo...

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Autores principales: Grace, Christopher, Hopewell, Jemma C., Watkins, Hugh, Farrall, Martin, Goel, Anuj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983061/
https://www.ncbi.nlm.nih.gov/pubmed/34672391
http://dx.doi.org/10.1002/gepi.22434
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author Grace, Christopher
Hopewell, Jemma C.
Watkins, Hugh
Farrall, Martin
Goel, Anuj
author_facet Grace, Christopher
Hopewell, Jemma C.
Watkins, Hugh
Farrall, Martin
Goel, Anuj
author_sort Grace, Christopher
collection PubMed
description Type 2 diabetes (T2D) is an important heritable risk factor for coronary artery disease (CAD), the risk of both diseases being increased by metabolic syndrome (MS). With the availability of large‐scale genome‐wide association data, we aimed to elucidate the genetic burden of CAD risk in T2D predisposed individuals within the context of MS and their shared genetic architecture. Mendelian randomization (MR) analyses supported a causal relationship between T2D and CAD [odds ratio (OR) = 1.13 per log‐odds unit 95% confidence interval (CI): 1.10–1.16; p = 1.59 × 10(−17)]. Simultaneously adjusting MR analyses for the effects of the T2D instrument including blood pressure, dyslipidaemia, and obesity attenuated the association between T2D and CAD (OR = 1.07, 95% CI: 1.04–1.11). Bayesian locus‐overlap analysis identified 44 regions with the same causal variant underlying T2D and CAD genetic signals (FDR < 1%) at a posterior probability >0.7; five (MHC, LPL, ABO, RAI1 and MC4R) of these regions contain genome‐wide significant (p < 5 × 10(−8)) associations for both traits. Given the small effect sizes observed in genome‐wide association studies for complex diseases, even with 44 potential target regions, this has implications for the likely magnitude of CAD risk reduction that might be achievable by pure T2D therapies.
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spelling pubmed-89830612022-04-11 Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes Grace, Christopher Hopewell, Jemma C. Watkins, Hugh Farrall, Martin Goel, Anuj Genet Epidemiol Research Articles Type 2 diabetes (T2D) is an important heritable risk factor for coronary artery disease (CAD), the risk of both diseases being increased by metabolic syndrome (MS). With the availability of large‐scale genome‐wide association data, we aimed to elucidate the genetic burden of CAD risk in T2D predisposed individuals within the context of MS and their shared genetic architecture. Mendelian randomization (MR) analyses supported a causal relationship between T2D and CAD [odds ratio (OR) = 1.13 per log‐odds unit 95% confidence interval (CI): 1.10–1.16; p = 1.59 × 10(−17)]. Simultaneously adjusting MR analyses for the effects of the T2D instrument including blood pressure, dyslipidaemia, and obesity attenuated the association between T2D and CAD (OR = 1.07, 95% CI: 1.04–1.11). Bayesian locus‐overlap analysis identified 44 regions with the same causal variant underlying T2D and CAD genetic signals (FDR < 1%) at a posterior probability >0.7; five (MHC, LPL, ABO, RAI1 and MC4R) of these regions contain genome‐wide significant (p < 5 × 10(−8)) associations for both traits. Given the small effect sizes observed in genome‐wide association studies for complex diseases, even with 44 potential target regions, this has implications for the likely magnitude of CAD risk reduction that might be achievable by pure T2D therapies. John Wiley and Sons Inc. 2021-10-21 2022-02 /pmc/articles/PMC8983061/ /pubmed/34672391 http://dx.doi.org/10.1002/gepi.22434 Text en © 2021 The Authors. Genetic Epidemiology published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Grace, Christopher
Hopewell, Jemma C.
Watkins, Hugh
Farrall, Martin
Goel, Anuj
Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
title Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
title_full Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
title_fullStr Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
title_full_unstemmed Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
title_short Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
title_sort robust estimates of heritable coronary disease risk in individuals with type 2 diabetes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983061/
https://www.ncbi.nlm.nih.gov/pubmed/34672391
http://dx.doi.org/10.1002/gepi.22434
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