{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:08:04Z","timestamp":1777943284285,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23NS086873"],"award-info":[{"award-number":["K23NS086873"]}],"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":["R01NS103924"],"award-info":[{"award-number":["R01NS103924"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Stroke"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and aims:<\/jats:title>\n                    <jats:p>Combining biologically related traits in genome-wide association studies (GWAS) increases the power for genetic discovery. Given the established relationship between lobar intracerebral hemorrhage (ICH) and cerebral amyloid angiopathy (CAA), and between the latter and levels of cerebrospinal fluid amyloid-\u03b2 42 (CSF-A\u03b242), we leveraged genetic predisposition for lower CSF-A\u03b242 levels as a proxy phenotype for CAA to identify new genes associated with lobar ICH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We used publicly available GWAS data for CSF-A\u03b242 levels (n\u2009=\u20093146) and for lobar ICH (n\u2009=\u20092094). First, we evaluated the association between lobar ICH risk and CSF-A\u03b242 in lobar ICH patients using a polygenic risk score (PRS) for CSF-A\u03b242. Next, we conducted multi-trait analysis of GWAS (MTAG) for pleiotropy analysis of lobar ICH and CSF-A\u03b242. MTAG results were further tested using Expression Quantitative Trait Locus and Differential Gene Expression Analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      CSF-A\u03b242 PRS was associated with lobar ICH risk (p\u2009=\u20090.04). MTAG analysis identified a novel association within CDH9 (rs1007589; minor allele frequency\u2009=\u20090.09; MTAG p\u2009=\u20095.4 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      ; lobar ICH odds ratio\u2009=\u20091.4 and p\u2009=\u20092.4 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ; CSF-A\u03b242 \u03b2\u2009=\u2009\u22120.03 and p\u2009=\u20094.5 \u00d7 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). rs1007589 was significantly associated with the expression levels of CDH9 in temporal and occipital cortices, regions known to preferentially accumulate microhemorrhages in CAA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our pleiotropy analysis suggested a variant possibly implicated with lobar ICH driven by amyloid-related mechanisms in CDH9 and associated with differential expression in brain regions characteristically affected by CAA. CDH9 is one subtype of the cadherin superfamily, which regulates intercellular adhesion, is involved in blood-brain barrier integrity, and is elevated in Alzheimer\u2019s disease patients. Further analyses are warranted to understand the effects of the variant on the pathogenesis of ICH and its clinical significance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17474930231155816","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T08:14:31Z","timestamp":1674807271000},"page":"804-811","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Pleiotropy analysis between lobar intracerebral hemorrhage and CSF \u03b2-amyloid highlights new and established associations"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1702-8168","authenticated-orcid":false,"given":"Sandro","family":"Marini","sequence":"first","affiliation":[{"name":"Department of Neurology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-9454","authenticated-orcid":false,"given":"Jaeyoon","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xudong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0605-2381","authenticated-orcid":false,"given":"Livia","family":"Parodi","sequence":"additional","affiliation":[{"name":"McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay A","family":"Farrer","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA"},{"name":"NHLBI\u2019s Framingham Heart Study, Framingham, MA, USA"},{"name":"Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Rosand","sequence":"additional","affiliation":[{"name":"McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Rafael","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA"},{"name":"NHLBI\u2019s Framingham Heart Study, Framingham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher D","family":"Anderson","sequence":"additional","affiliation":[{"name":"McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA"},{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"bibr1-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649503"},{"key":"bibr2-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70104-7"},{"key":"bibr3-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0058-3"},{"key":"bibr4-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.02.012"},{"key":"bibr5-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz233"},{"key":"bibr6-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018922"},{"key":"bibr7-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009642"},{"key":"bibr8-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000143224.36527.44"},{"key":"bibr9-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005030"},{"key":"bibr10-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21694"},{"key":"bibr11-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1177\/1747493020974464"},{"key":"bibr12-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1685-y"},{"key":"bibr13-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09718-5"},{"key":"bibr14-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0009-4"},{"key":"bibr15-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03621-1"},{"key":"bibr16-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3801"},{"key":"bibr17-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00389-0"},{"key":"bibr18-17474930231155816","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201797397"},{"key":"bibr19-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2021.12.070"},{"key":"bibr20-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.005851"},{"key":"bibr21-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22516"},{"key":"bibr22-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.119"},{"key":"bibr23-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-012-0252-1"},{"key":"bibr24-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18774666"},{"key":"bibr25-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4519"},{"key":"bibr26-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2018.4550"},{"key":"bibr27-17474930231155816","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X16666180222164809"},{"key":"bibr28-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21681"},{"key":"bibr29-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.12.006"},{"key":"bibr30-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.593657"},{"key":"bibr31-17474930231155816","volume":"2017","author":"Van Nieuwenhuizen KM","year":"2017","journal-title":"BMJ Case Rep"},{"key":"bibr32-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl387"},{"key":"bibr33-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003183"},{"key":"bibr34-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010852"},{"key":"bibr35-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.07.028"},{"key":"bibr36-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65038-5"},{"key":"bibr37-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1038\/cddiscovery.2017.51"},{"key":"bibr38-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7139.1236"},{"key":"bibr39-17474930231155816","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0332-x"}],"container-title":["International Journal of Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17474930231155816","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17474930231155816","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17474930231155816","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:21:43Z","timestamp":1777706503000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17474930231155816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1177\/17474930231155816"],"URL":"https:\/\/doi.org\/10.1177\/17474930231155816","relation":{},"ISSN":["1747-4930","1747-4949"],"issn-type":[{"value":"1747-4930","type":"print"},{"value":"1747-4949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}