{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:04:26Z","timestamp":1786457066944,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 NS065705"],"award-info":[{"award-number":["U54 NS065705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U2CTR002818"],"award-info":[{"award-number":["U2CTR002818"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To investigate whether common variants in <jats:italic>EPHB4<\/jats:italic> and <jats:italic>RASA1<\/jats:italic> are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Familial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (<jats:italic>n<\/jats:italic>\u00a0=\u00a0338). Total lesions and large lesions (\u22655\u00a0mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome\u2010Wide LAT1 Human Array. We tested the association of seven common variants (three in <jats:italic>EPHB4<\/jats:italic> and four in <jats:italic>RASA1<\/jats:italic>) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05\/7 variants\u00a0=\u00a00.007).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>EPHB4<\/jats:italic> variants were not significantly associated with CCM severity phenotypes. One <jats:italic>RASA1<\/jats:italic> intronic variant (rs72783711 A&gt;C) was significantly associated with ICH (OR\u00a0=\u00a01.82, 95% CI\u00a0=\u00a01.21\u20132.37, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.004) and nominally associated with large lesion count (PI\u00a0=\u00a01.17, 95% CI\u00a0=\u00a01.03\u20131.32, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A common <jats:italic>RASA1<\/jats:italic> variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1794","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T11:34:16Z","timestamp":1631014456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessing the association of common genetic variants in <i>EPHB4<\/i> and <i>RASA1<\/i> with phenotype severity in familial cerebral cavernous malformation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-0227","authenticated-orcid":false,"given":"Foram","family":"Choksi","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco San Francisco California 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