{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:50:55Z","timestamp":1784307055232,"version":"3.55.0"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi231626-4\"><jats:title>Importance<\/jats:title><jats:p>Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in <jats:italic>APOE<\/jats:italic> \u03b54 carriers that may increase the risk of ICH.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231626-5\"><jats:title>Objective<\/jats:title><jats:p>To assess whether <jats:italic>APOE<\/jats:italic> \u03b54 is associated with a higher risk of ICH in patients with a known AVM.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231626-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated <jats:italic>International Classification of Diseases, Ninth Revision<\/jats:italic> and <jats:italic>Tenth Revision,<\/jats:italic> codes. Genotypic data on the <jats:italic>APOE<\/jats:italic> variants rs429358 and rs7412 were used to ascertain the \u03b5 status.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231626-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>For each study, the association between <jats:italic>APOE<\/jats:italic> \u03b54 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231626-8\"><jats:title>Results<\/jats:title><jats:p>The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, <jats:italic>APOE<\/jats:italic> \u03b54 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, <jats:italic>APOE<\/jats:italic> \u03b54 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; <jats:italic>P<\/jats:italic>\u2009=\u2009.03).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231626-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on <jats:italic>APOE<\/jats:italic> \u03b54 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.55368","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T16:30:59Z","timestamp":1708101059000},"page":"e2355368","source":"Crossref","is-referenced-by-count":4,"title":["<i>APOE<\/i> 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