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This large-scale genetic study brings together \u2018big data\u2019 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 CARDIoGRAM<jats:italic>plus<\/jats:italic>C4D and 17,008 LOAD cases from the IGAP Consortium. Additional analyses assessed the independent relevance of genetic associations at the <jats:italic>APOE<\/jats:italic> 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\u20131.15]; p\u2009=\u20090.027). However, after exclusion of the <jats:italic>APOE<\/jats:italic> locus, the estimate of the causal effect of CAD for LOAD was attenuated and no longer significant (OR 0.94 [0.88\u20131.01]; p\u2009=\u20090.072). This Mendelian randomization study indicates that the <jats:italic>APOE<\/jats:italic> 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 <jats:italic>APOE<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/s41598-018-25460-2","type":"journal-article","created":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T08:53:54Z","timestamp":1525164834000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"8","author":[{"given":"Christopher","family":"Grace","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-4021","authenticated-orcid":false,"given":"Anuj","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Farrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemma C.","family":"Hopewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,8]]},"reference":[{"key":"25460_CR1","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/35025203","volume":"407","author":"AJ Lusis","year":"2000","unstructured":"Lusis, A. 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