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Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

dc.rights.licenseopenen_US
dc.contributor.authorBAKKER, Mark R.
dc.contributor.authorKANNING, Jos P.
dc.contributor.authorABRAHAM, Gad
dc.contributor.authorMARTINSEN, Amy E.
dc.contributor.authorWINSVOLD, Bendik S.
dc.contributor.authorZWART, John-Anker
dc.contributor.authorBOURCIER, Romain
dc.contributor.authorSAWADA, Tomonobu
dc.contributor.authorKOIDO, Masaru
dc.contributor.authorKAMATANI, Yoichiro
dc.contributor.authorMOREL, Sandrine
dc.contributor.authorAMOUYEL, Philippe
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorBIJLENGA, Philippe
dc.contributor.authorBERRANDOU, Takiy
dc.contributor.authorGANESH, Santhi K.
dc.contributor.authorBOUATIA-NAJI, Nabila
dc.contributor.authorJONES, Gregory
dc.contributor.authorBOWN, Matthew
dc.contributor.authorRINKEL, Gabriel J. E.
dc.contributor.authorVELDINK, Jan H.
dc.contributor.authorRUIGROK, Ynte M.
dc.date.accessioned2023-02-21T17:19:15Z
dc.date.available2023-02-21T17:19:15Z
dc.date.issued2023-01-19
dc.identifier.issn0039-2499en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/172040
dc.description.abstractEnBACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10(-3) per year [95% CI, -6.49×10(-3) to -3.14×10(-3)]; P=1.82×10(-8)), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enAneurysmal subarachnoid hemorrhage
dc.subject.enRisk assessment
dc.subject.enGenetics
dc.subject.enGenetic heterogeneity
dc.subject.enIntracranial aneurysm
dc.title.enGenetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity
dc.title.alternativeStrokeen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/strokeaha.122.040715en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed36655558en_US
bordeaux.journalStrokeen_US
bordeaux.page810-818
bordeaux.volume54
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue3
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03999672
hal.version1
hal.date.transferred2023-02-21T17:19:43Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Stroke&rft.date=2023-01-19&rft.volume=54&rft.issue=3&rft.spage=810-818&rft.epage=810-818&rft.eissn=0039-2499&rft.issn=0039-2499&rft.au=BAKKER,%20Mark%20R.&KANNING,%20Jos%20P.&ABRAHAM,%20Gad&MARTINSEN,%20Amy%20E.&WINSVOLD,%20Bendik%20S.&rft.genre=article


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