{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:28:03Z","timestamp":1786976883491,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,30]],"date-time":"2016-03-30T00:00:00Z","timestamp":1459296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000364","name":"Stroke Association","doi-asserted-by":"crossref","award":["TSA 2013\/01 and TSA 2010\/10"],"award-info":[{"award-number":["TSA 2013\/01 and TSA 2010\/10"]}],"id":[{"id":"10.13039\/501100000364","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MRC\/Stroke Association"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research (NIHR)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wellcome Trust"},{"name":"Collection of the UK Young Lacunar Stroke DNA Study","award":["WT072952"],"award-info":[{"award-number":["WT072952"]}]},{"name":"NIHR Comprehensive Biomedical Research Unit at Cambridge University Hospitals Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and ischemic stroke (IS). We investigated the evidence that shared genetic factors underpin the two diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using genome\u2010wide association study (GWAS) data from METASTROKE\u2009+\u2009(15,916 IS cases and 68,826 controls) and the International Genomics of Alzheimer's Project (IGAP; 17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype\u2010level data (4,610 IS cases, 1,281 AD cases, and 14,320 controls), we estimated the genome\u2010wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, and large vessel), using genome\u2010wide single\u2010nucleotide polymorphism (SNP) data. We then performed a meta\u2010analysis and pathway analysis in the combined AD and small vessel stroke data sets to identify the SNPs and molecular pathways through which disease risk may be conferred.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found evidence of a shared genetic contribution between AD and small vessel stroke (rG [standard error]\u2009=\u20090.37 [0.17];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta\u2010analysis of AD IGAP and METASTROKE\u2009+\u2009small vessel stroke GWAS data highlighted a region (ATP5H\/KCTD2\/ICT1) associated with both diseases (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.8\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). A pathway analysis identified four associated pathways involving cholesterol transport and immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. Ann Neurol 2016;79:739\u2013747<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24621","type":"journal-article","created":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T22:17:06Z","timestamp":1456438626000},"page":"739-747","source":"Crossref","is-referenced-by-count":69,"title":["Shared genetic contribution to ischemic stroke and Alzheimer's disease"],"prefix":"10.1002","volume":"79","author":[{"given":"Matthew","family":"Traylor","sequence":"first","affiliation":[{"name":"Stroke Research Group, Department of Clinical Neurosciences University of Cambridge Cambridge United Kingdom"},{"name":"Department of Medical &amp; Molecular Genetics King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poneh","family":"Adib\u2010Samii","sequence":"additional","affiliation":[{"name":"Stroke and Dementia Research Center St George's University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Harold","sequence":"additional","affiliation":[{"name":"School of Biotechnology Dublin City University Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Alzheimer's Disease Neuroimaging Initiative, The International Stroke Genetics Consortium (ISGC), UK Young Lacunar Stroke DNA resource","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dichgans","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research Klinikum der Universit\u00e4t M\u00fcnchen, Ludwig\u2010Maximilians\u2010Universit\u00e4t Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Williams","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Center for 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