Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease

Abstract Epidemiological studies suggest a positive association between coronary artery disease (CAD) and late-onset Alzheimer’s disease (LOAD). This large-scale genetic study brings together ‘big data’ resources to examine the causal impact of genetic determinants of CAD on risk of LOAD. A two-samp...

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Autores principales:	Christopher Grace, Robert Clarke, Anuj Goel, Martin Farrall, Hugh Watkins, Jemma C. Hopewell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2cb8fb5b7bb44d792d108e952263d43
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spelling	oai:doaj.org-article:e2cb8fb5b7bb44d792d108e952263d432021-12-02T16:07:51ZLack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease10.1038/s41598-018-25460-22045-2322https://doaj.org/article/e2cb8fb5b7bb44d792d108e952263d432018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25460-2https://doaj.org/toc/2045-2322Abstract Epidemiological studies suggest a positive association between coronary artery disease (CAD) and late-onset Alzheimer’s disease (LOAD). This large-scale genetic study brings together ‘big data’ resources to examine the causal impact of genetic determinants of CAD on risk of LOAD. A two-sample Mendelian randomization approach was adopted to estimate the causal effect of CAD on risk of LOAD using summary data from 60,801 CAD cases from CARDIoGRAMplusC4D and 17,008 LOAD cases from the IGAP Consortium. Additional analyses assessed the independent relevance of genetic associations at the APOE locus for both CAD and LOAD. Higher genetically determined risk of CAD was associated with a slightly higher risk of LOAD (Odds Ratio (OR) per log-odds unit of CAD [95% CI]: 1.07 [1.01–1.15]; p = 0.027). However, after exclusion of the APOE locus, the estimate of the causal effect of CAD for LOAD was attenuated and no longer significant (OR 0.94 [0.88–1.01]; p = 0.072). This Mendelian randomization study indicates that the APOE locus is the chief determinant of shared genetic architecture between CAD and LOAD, and suggests a lack of causal relevance of CAD for risk of LOAD after exclusion of APOE.Christopher GraceRobert ClarkeAnuj GoelMartin FarrallHugh WatkinsJemma C. HopewellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher Grace Robert Clarke Anuj Goel Martin Farrall Hugh Watkins Jemma C. Hopewell Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
description	Abstract Epidemiological studies suggest a positive association between coronary artery disease (CAD) and late-onset Alzheimer’s disease (LOAD). This large-scale genetic study brings together ‘big data’ resources to examine the causal impact of genetic determinants of CAD on risk of LOAD. A two-sample Mendelian randomization approach was adopted to estimate the causal effect of CAD on risk of LOAD using summary data from 60,801 CAD cases from CARDIoGRAMplusC4D and 17,008 LOAD cases from the IGAP Consortium. Additional analyses assessed the independent relevance of genetic associations at the APOE locus for both CAD and LOAD. Higher genetically determined risk of CAD was associated with a slightly higher risk of LOAD (Odds Ratio (OR) per log-odds unit of CAD [95% CI]: 1.07 [1.01–1.15]; p = 0.027). However, after exclusion of the APOE locus, the estimate of the causal effect of CAD for LOAD was attenuated and no longer significant (OR 0.94 [0.88–1.01]; p = 0.072). This Mendelian randomization study indicates that the APOE locus is the chief determinant of shared genetic architecture between CAD and LOAD, and suggests a lack of causal relevance of CAD for risk of LOAD after exclusion of APOE.
format	article
author	Christopher Grace Robert Clarke Anuj Goel Martin Farrall Hugh Watkins Jemma C. Hopewell
author_facet	Christopher Grace Robert Clarke Anuj Goel Martin Farrall Hugh Watkins Jemma C. Hopewell
author_sort	Christopher Grace
title	Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
title_short	Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
title_full	Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
title_fullStr	Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
title_full_unstemmed	Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
title_sort	lack of genetic support for shared aetiology of coronary artery disease and late-onset alzheimer’s disease
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e2cb8fb5b7bb44d792d108e952263d43
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Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease

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