{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:51:25Z","timestamp":1782273085553,"version":"3.54.5"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Intracerebral hemorrhage (ICH) is the most devastating adverse outcome for patients on anticoagulants. Clinical risk scores that quantify bleeding risk can guide decision-making in situations when indication or duration for anticoagulation is uncertain. We investigated whether integration of a genetic risk score into an existing risk factor\u2013based CRS could improve risk stratification for anticoagulation-related ICH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We constructed 153 genetic risk scores from genome-wide association data of 1545 ICH cases and 1481 controls and validated them in 431 ICH cases and 431 matched controls from the population-based UK Biobank. The score that explained the largest variance in ICH risk was selected and tested for prediction of incident ICH in an independent cohort of 5530 anticoagulant users. A CRS for major anticoagulation-related hemorrhage, based on 8\/9 components of the HAS-BLED score, was compared with a combined clinical and genetic risk score incorporating an additional point for high genetic risk for ICH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among anticoagulated individuals, 94 ICH occurred over a mean follow-up of 11.9 years. Compared with the lowest genetic risk score tertile, being in the highest tertile was associated with a two-fold increased risk for incident ICH (hazard ratio, 2.08 [95% CI, 1.22\u20133.56]). Although the CRS predicted incident ICH with a hazard ratio of 1.24 per 1-point increase (95% CI [1.01\u20131.53]), adding a point for high genetic ICH risk led to a stronger association (hazard ratio of 1.33 per 1-point increase [95% CI, 1.11\u20131.59]) with improved risk stratification (C index 0.57 versus 0.53) and maintained calibration (integrated calibration index 0.001 for both). The new clinical and genetic risk score showed 19% improvement in high-risk classification among individuals with ICH and a net reclassification improvement of 0.10.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Among anticoagulant users, a prediction score incorporating genomic information is superior to a clinical risk score alone for ICH risk stratification and could serve in clinical decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.122.041764","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T05:07:59Z","timestamp":1675919279000},"page":"791-799","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Risk Score Improves Risk Stratification for Anticoagulation-Related Intracerebral Hemorrhage"],"prefix":"10.1161","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-4209","authenticated-orcid":true,"given":"Ernst","family":"Mayerhofer","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Henry and Allison McCance Center for Brain Health (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge (E.M., L.P., S.P., J.R., M.K.G., C.D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0605-2381","authenticated-orcid":true,"given":"Livia","family":"Parodi","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Henry and Allison McCance Center for Brain Health (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge (E.M., L.P., S.P., J.R., M.K.G., C.D.A.)."},{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA (L.P., C.D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-2566","authenticated-orcid":true,"given":"Savvina","family":"Prapiadou","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Henry and Allison McCance Center for Brain Health (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge (E.M., L.P., S.P., J.R., M.K.G., C.D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9212-2520","authenticated-orcid":true,"given":"Rainer","family":"Malik","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University Munich, Germany (R.M., M.K.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-9138","authenticated-orcid":true,"given":"Jonathan","family":"Rosand","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Henry and Allison McCance Center for Brain Health (E.M., L.P., S.P., J.R., M.K.G., C.D.A.), Massachusetts General Hospital, Boston."},{"name":"Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute 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