{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:21:50Z","timestamp":1721953310726},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180"],"award-info":[{"award-number":["No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180","No. 8227052180"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan university.","award":["none","none","none","none","none","none","none","none","none","none","none"],"award-info":[{"award-number":["none","none","none","none","none","none","none","none","none","none","none"]}]},{"name":"The Cerebrovascular Disease Management Project of Sailing Foundation of China Stroke Association.","award":["none","none","none","none","none","none","none","none","none","none","none"],"award-info":[{"award-number":["none","none","none","none","none","none","none","none","none","none","none"]}]},{"name":"Heart and Brain Health Public Welfare Project of Buchang Zhiyuan Foundation","award":["NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107"],"award-info":[{"award-number":["NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107","NO. HIGHER2022107"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"Abstract<\/jats:title>\n Objective<\/jats:title>\n Cerebral artery dissection (CeAD) is a rare but serious disease. Genetic risk assessment for CeAD is lacking in Chinese population. We performed genome-wide association study (GWAS) and computed polygenic risk score (PRS) to explore genetic susceptibility factors and prediction model of CeAD based on patients in Huashan Hospital.<\/jats:p>\n <\/jats:sec>\n Methods<\/jats:title>\n A total of 210 CeAD patients and 280 controls were enrolled from June 2017 to September 2022 in Department of Neurology, Huashan Hospital, Fudan University. We performed GWAS to identify genetic variants associated with CeAD in 140 CeAD patients and 210 control individuals according to a case and control 1:1.5 design rule in the training dataset, while the other 70 patients with CeAD and 70 controls were used as validation. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were utilized to identify the significant pathways. We constructed a PRS by capturing all independent GWAS SNPs in the analysis and explored the predictivity of PRS, age, and sex for CeAD.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n Through GWAS analysis of the 140 cases and 210 controls in the training dataset, we identified 13 leading SNPs associated with CeAD at a genome-wide significance level of P<\/jats:italic>\u2009<\u20095\u2009\u00d7\u200910\u2212\u20098<\/jats:sup>. Among them, 10 SNPs were annotated in or near (in the upstream and downstream regions of \u00b1\u2009500Kb) 10 functional genes. rs34508376 (OR2L13) played a suggestive role in CeAD pathophysiology which was in line with previous observations in aortic aneurysms. The other nine genes were first-time associations in CeAD cases. GO enrichment analyses showed that these 10 genes have known roles in 20 important GO terms clustered into two groups: (1) cellular biological processes (BP); (2) molecular function (MF). We used genome-wide association data to compute PRS including 32 independent SNPs and constructed predictive model for CeAD by using age, sex and PRS as predictors both in training and validation test. The area under curve (AUC) of PRS predictive model for CeAD reached 99% and 95% in the training test and validation test respectively, which were significantly larger than the age and sex models of 83% and 86%.<\/jats:p>\n <\/jats:sec>\n Conclusions<\/jats:title>\n Our study showed that ten risk loci were associated with CeAD susceptibility, and annotated functional genes had roles in 20 important GO terms clustered into biological process and molecular function. The PRS derived from risk variants was associated with CeAD incidence after adjusting for age and sex both in training test and validation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12883-024-03759-0","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T09:02:43Z","timestamp":1721898163000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GWAS-based polygenic risk scoring for predicting cerebral artery dissection in the Chinese population"],"prefix":"10.1186","volume":"24","author":[{"given":"Shufan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongliang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanzeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaocui","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingdong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Suo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"issue":"11","key":"3759_CR1","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/S1474-4422(10)70251-9","volume":"9","author":"JM Ferro","year":"2010","unstructured":"Ferro JM, Massaro AR, Mas JL. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol. 2010;9(11):1085\u201396.","journal-title":"Lancet Neurol"},{"issue":"6","key":"3759_CR2","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1148\/rg.2019190033","volume":"39","author":"JL McCarty","year":"2019","unstructured":"McCarty JL, et al. Ischemic infarction in young adults: a review for radiologists. Radiographics. 2019;39(6):1629\u201348.","journal-title":"Radiographics"},{"issue":"12","key":"3759_CR3","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","volume":"137","author":"EJ Benjamin","year":"2018","unstructured":"Benjamin EJ, et al. Heart Disease and Stroke Statistics-2018 update: a Report from the American Heart Association. Circulation. 2018;137(12):e67\u2013492.","journal-title":"Circulation"},{"issue":"21","key":"3759_CR4","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1212\/WNL.0b013e318293e2eb","volume":"80","author":"ST Engelter","year":"2013","unstructured":"Engelter ST, et al. Cervical artery dissection: trauma and other potential mechanical trigger events. Neurology. 2013;80(21):1950\u20137.","journal-title":"Neurology"},{"issue":"6","key":"3759_CR5","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.jacc.2018.04.089","volume":"72","author":"M Renard","year":"2018","unstructured":"Renard M, et al. Clinical validity of genes for heritable thoracic aortic aneurysm and dissection. J Am Coll Cardiol. 2018;72(6):605\u201315.","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"3759_CR6","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1161\/CIRCRESAHA.118.312436","volume":"124","author":"A Pinard","year":"2019","unstructured":"Pinard A, Jones GT, Milewicz DM. Genetics of thoracic and abdominal aortic diseases. Circ Res. 2019;124(4):588\u2013606.","journal-title":"Circ Res"},{"issue":"2","key":"3759_CR7","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1161\/STROKEAHA.118.021856","volume":"50","author":"D Pfeiffer","year":"2019","unstructured":"Pfeiffer D, et al. Genetic imbalance is Associated with Functional Outcome after ischemic stroke. Stroke. 2019;50(2):298\u2013304.","journal-title":"Stroke"},{"issue":"2","key":"3759_CR8","doi-asserted-by":"publisher","first-page":"206","DOI":"10.2174\/1389202917666160805152627","volume":"18","author":"C Grond-Ginsbach","year":"2017","unstructured":"Grond-Ginsbach C, et al. Genetic imbalance in patients with cervical artery dissection. Curr Genomics. 2017;18(2):206\u201313.","journal-title":"Curr Genomics"},{"issue":"1","key":"3759_CR9","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/ng.3154","volume":"47","author":"S Debette","year":"2015","unstructured":"Debette S, et al. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. Nat Genet. 2015;47(1):78\u201383.","journal-title":"Nat Genet"},{"issue":"1","key":"3759_CR10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12883-018-1011-x","volume":"18","author":"Z Zhu","year":"2018","unstructured":"Zhu Z, et al. Chinese cervicocephalic artery dissection study (CCADS): rationale and protocol for a multicenter prospective cohort study. BMC Neurol. 2018;18(1):6.","journal-title":"BMC Neurol"},{"issue":"14","key":"3759_CR11","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754\u201360.","journal-title":"Bioinformatics"},{"key":"3759_CR12","doi-asserted-by":"crossref","unstructured":"Danecek P et al. Twelve years of SAMtools and BCFtools. Gigascience, 2021. 10(2).","DOI":"10.1093\/gigascience\/giab008"},{"issue":"7886","key":"3759_CR13","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/s41586-021-04103-z","volume":"599","author":"JD Backman","year":"2021","unstructured":"Backman JD, et al. Exome sequencing and analysis of 454,787 UK Biobank participants. Nature. 2021;599(7886):628\u201334.","journal-title":"Nature"},{"issue":"3","key":"3759_CR14","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559\u201375.","journal-title":"Am J Hum Genet"},{"issue":"6","key":"3759_CR15","doi-asserted-by":"publisher","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","volume":"5","author":"BN Howie","year":"2009","unstructured":"Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009;5(6):e1000529.","journal-title":"PLoS Genet"},{"issue":"2","key":"3759_CR16","doi-asserted-by":"publisher","first-page":"e1608","DOI":"10.1002\/mpr.1608","volume":"27","author":"AT Marees","year":"2018","unstructured":"Marees AT, et al. A tutorial on conducting genome-wide association studies: quality control and statistical analysis. Int J Methods Psychiatr Res. 2018;27(2):e1608.","journal-title":"Int J Methods Psychiatr Res"},{"issue":"3","key":"3759_CR17","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1111\/j.1541-0420.2010.01520.x","volume":"67","author":"S Lee","year":"2011","unstructured":"Lee S, Wright FA, Zou F. Control of population stratification by correlation-selected principal components. Biometrics. 2011;67(3):967\u201374.","journal-title":"Biometrics"},{"issue":"R2","key":"3759_CR18","doi-asserted-by":"publisher","first-page":"R133","DOI":"10.1093\/hmg\/ddz187","volume":"28","author":"SA Lambert","year":"2019","unstructured":"Lambert SA, Abraham G, Inouye M. Towards clinical utility of polygenic risk scores. Hum Mol Genet. 2019;28(R2):R133\u201342.","journal-title":"Hum Mol Genet"},{"issue":"1","key":"3759_CR19","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13073-020-00742-5","volume":"12","author":"M LEWIS C","year":"2020","unstructured":"LEWIS C M. Polygenic risk scores: from research tools to clinical instruments[J]. Genome Med. 2020;12(1):44.","journal-title":"Genome Med"},{"key":"3759_CR20","doi-asserted-by":"crossref","unstructured":"Morrell CN et al. Platelet olfactory receptor activation limits platelet reactivity and growth of aortic aneurysms. J Clin Invest, 2022. 132(9).","DOI":"10.1172\/JCI152373"},{"issue":"2","key":"3759_CR21","first-page":"540","volume":"29","author":"OS Salehi","year":"2023","unstructured":"Salehi OS. Cervical artery dissection. Continuum (Minneap Minn). 2023;29(2):540\u201365.","journal-title":"Continuum (Minneap Minn)"},{"issue":"8","key":"3759_CR22","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1007\/s00415-011-6395-0","volume":"259","author":"M Kloss","year":"2012","unstructured":"Kloss M, et al. Towards understanding seasonal variability in cervical artery dissection (CeAD). J Neurol. 2012;259(8):1662\u20137.","journal-title":"J Neurol"},{"issue":"16","key":"3759_CR23","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1212\/WNL.0b013e318251595f","volume":"78","author":"TM Metso","year":"2012","unstructured":"Metso TM, et al. Migraine in cervical artery dissection and ischemic stroke patients. Neurology. 2012;78(16):1221\u20138.","journal-title":"Neurology"},{"issue":"2","key":"3759_CR24","doi-asserted-by":"publisher","first-page":"210","DOI":"10.2174\/156652409787581547","volume":"9","author":"C Grond-Ginsbach","year":"2009","unstructured":"Grond-Ginsbach C, Debette S. The association of connective tissue disorders with cervical artery dissections. Curr Mol Med. 2009;9(2):210\u20134.","journal-title":"Curr Mol Med"},{"key":"3759_CR25","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/978-3-030-80614-9_8","volume":"1348","author":"SM Zeigler","year":"2021","unstructured":"Zeigler SM, Sloan B, Jones JA. Pathophysiology and Pathogenesis of Marfan Syndrome. Adv Exp Med Biol. 2021;1348:185\u2013206.","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"3759_CR26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cjca.2015.11.004","volume":"32","author":"A Karimi","year":"2016","unstructured":"Karimi A, Milewicz DM. Structure of the elastin-contractile units in the thoracic aorta and how genes that cause thoracic aortic aneurysms and dissections disrupt this structure. Can J Cardiol. 2016;32(1):26\u201334.","journal-title":"Can J Cardiol"},{"key":"3759_CR27","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.ebiom.2019.09.041","volume":"49","author":"G Lian","year":"2019","unstructured":"Lian G, et al. Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1\u03b1-ADAM17 pathway(). EBioMedicine. 2019;49:291\u2013304.","journal-title":"EBioMedicine"},{"key":"3759_CR28","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.mehy.2018.09.039","volume":"121","author":"A Pitliya","year":"2018","unstructured":"Pitliya A, et al. Eosinophilic inflammation in spontaneous coronary artery dissection: a potential therapeutic target? Med Hypotheses. 2018;121:91\u20134.","journal-title":"Med Hypotheses"},{"issue":"12","key":"3759_CR29","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1007\/s00415-011-6089-7","volume":"258","author":"J van Gaalen","year":"2011","unstructured":"van Gaalen J, et al. Dissection of the posterior inferior cerebellar artery in the hypereosinophilic syndrome. J Neurol. 2011;258(12):2278\u201380.","journal-title":"J Neurol"},{"issue":"9","key":"3759_CR30","doi-asserted-by":"publisher","first-page":"6819","DOI":"10.1074\/jbc.M111.293365","volume":"287","author":"H Luo","year":"2012","unstructured":"Luo H, et al. Receptor tyrosine kinase Ephb6 regulates vascular smooth muscle contractility and modulates blood pressure in concert with sex hormones. J Biol Chem. 2012;287(9):6819\u201329.","journal-title":"J Biol Chem"},{"issue":"2","key":"3759_CR31","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1177\/147323001103900220","volume":"39","author":"A Sakamoto","year":"2011","unstructured":"Sakamoto A, et al. Expression profiling of the ephrin (EFN) and eph receptor (EPH) family of genes in atherosclerosis-related human cells. J Int Med Res. 2011;39(2):522\u20137.","journal-title":"J Int Med Res"},{"issue":"1","key":"3759_CR32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s12031-014-0312-9","volume":"55","author":"L Hongge","year":"2015","unstructured":"Hongge L, et al. The role of LRRK2 in the regulation of monocyte adhesion to endothelial cells. J Mol Neurosci. 2015;55(1):233\u20139.","journal-title":"J Mol Neurosci"},{"issue":"6","key":"3759_CR33","doi-asserted-by":"publisher","first-page":"e003030","DOI":"10.1161\/CIRCGEN.120.003030","volume":"13","author":"KJ Carss","year":"2020","unstructured":"Carss KJ, et al. Spontaneous coronary artery dissection: insights on Rare genetic variation from genome sequencing. Circ Genom Precis Med. 2020;13(6):e003030.","journal-title":"Circ Genom Precis Med"},{"issue":"6","key":"3759_CR34","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1681\/ASN.2018090909","volume":"30","author":"S Cameron-Christie","year":"2019","unstructured":"Cameron-Christie S, et al. Exome-based rare-variant analyses in CKD. J Am Soc Nephrol. 2019;30(6):1109\u201322.","journal-title":"J Am Soc Nephrol"},{"issue":"1","key":"3759_CR35","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1164\/rccm.201610-2088OC","volume":"196","author":"S Petrovski","year":"2017","unstructured":"Petrovski S, et al. An exome sequencing study to assess the role of Rare Genetic Variation in Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017;196(1):82\u201393.","journal-title":"Am J Respir Crit Care Med"},{"issue":"12","key":"3759_CR36","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1038\/s41588-020-00725-7","volume":"52","author":"MK Bakker","year":"2020","unstructured":"Bakker MK, et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet. 2020;52(12):1303\u201313.","journal-title":"Nat Genet"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-024-03759-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-024-03759-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-024-03759-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T09:04:16Z","timestamp":1721898256000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-024-03759-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3759"],"URL":"https:\/\/doi.org\/10.1186\/s12883-024-03759-0","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,25]]},"assertion":[{"value":"26 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Prior to the start of the research, all enrolled individuals signed informed consent. The study conformed to the principles of the declaration of Helsinki and was approved by the Internal Review Board of Huashan Hospital (HIRB) affiliated to Fudan University. The reference number was 2021-040.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"258"}}