{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T23:22:21Z","timestamp":1782516141004,"version":"3.54.5"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Genetic and nongenetic factors account for the association of family history with disease risk. Comparing adopted and nonadopted individuals provides an opportunity to disentangle those factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We examined associations between family history of stroke and heart disease with incident stroke and myocardial infarction (MI) in 495\u2009640 UK Biobank participants (mean age, 56.5\u2009years; 55% women) stratified by childhood adoption status (5747 adoptees). We estimated hazard ratios (HRs) per affected family member, and for polygenic risk scores in Cox models adjusted for baseline age and sex. A total of 12\u2009518 strokes and 23\u2009923 MIs occurred over a 13\u2010year follow\u2010up. In nonadoptees, family history of stroke and heart disease was associated with increased stroke and MI risk, with the strongest association of family history of stroke for incident stroke (HR, 1.16 [95% CI, 1.12\u20131.19]) and family history of heart disease for incident MI (HR, 1.48 [95% CI, 1.45\u20131.50]). In adoptees, family history of stroke associated with incident stroke (HR, 1.41 [95% CI, 1.06\u20131.86]), but family history of heart disease was not associated with incident MI (\n              <jats:italic>P<\/jats:italic>\n              &gt;0.5). Polygenic risk scores showed strong disease\u2010specific associations in both groups. In nonadoptees, the stroke polygenic risk score mediated 6% risk between family history of stroke and incident stroke, and the MI polygenic risk score mediated 13% risk between family history of heart disease and incident MI.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Family history of stroke and heart disease increases risk for their respective conditions. Family history of stroke contains substantial potentially modifiable nongenetic risk, indicating a need for novel prevention strategies, whereas family history of heart disease represents predominantly genetic risk.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.031566","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:17:02Z","timestamp":1697192222000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic and Nongenetic Components of Stroke Family History: A Population Study of Adopted and Nonadopted Individuals"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-4209","authenticated-orcid":false,"given":"Ernst","family":"Mayerhofer","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital Boston MA"},{"name":"Program in Medical and Population Genetics Broad Institute of 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Massachusetts General Hospital Boston MA"},{"name":"Program in Medical and Population Genetics Broad Institute of Harvard and the Massachusetts Institute of Technology Cambridge MA"},{"name":"McCance Center for Brain Health Massachusetts General Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-7910","authenticated-orcid":false,"given":"Andreas","family":"Harloff","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Medical Center\u2013University of Freiburg, Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3507-3659","authenticated-orcid":false,"given":"Marios K.","family":"Georgakis","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital Boston MA"},{"name":"Program in Medical and Population Genetics Broad Institute of Harvard and the Massachusetts Institute of Technology Cambridge MA"},{"name":"McCance Center for Brain Health Massachusetts General Hospital Boston MA"},{"name":"Institute for Stroke and Dementia Research University Hospital, Ludwig\u2010Maximilians\u2010University Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-9138","authenticated-orcid":false,"given":"Jonathan","family":"Rosand","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital Boston MA"},{"name":"Program in Medical and Population Genetics Broad Institute of Harvard and the Massachusetts Institute of Technology Cambridge MA"},{"name":"McCance Center for Brain Health Massachusetts General Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0053-2002","authenticated-orcid":false,"given":"Christopher 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