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Genetic Variants Underlying Risk of Intracranial Aneurysms: Insights from a GWAS in Portugal

2015-07-17Journal article Open access
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dc.contributor.authorAbrantes, Patrícia
dc.contributor.authorSantos, Maria M.
dc.contributor.authorSousa, Inês
dc.contributor.authorXavier, Joana M.
dc.contributor.authorFrancisco, Vânia
dc.contributor.authorKrug, Tiago
dc.contributor.authorSobral, João
dc.contributor.authorMatos, Mafalda
dc.contributor.authorMartins, Madalena
dc.contributor.authorJacinto, António
dc.contributor.authorCoiteiro, Domingos
dc.contributor.authorOliveira, Sofia A.
dc.date.accessioned2015-10-16T09:01:17Z
dc.date.available2015-10-16T09:01:17Z
dc.date.issued2015-07-17
dc.description.abstractSubarachnoid hemorrhage (SAH) is a life-threatening event that most frequently leads to severe disability and death. Its most frequent cause is the rupture of a saccular intracranial aneurysm (IA), which is a blood vessel dilation caused by disease or weakening of the vessel wall. Although the genetic contribution to IA is well established, to date no single gene has been unequivocally identified as responsible for IA formation or rupture. We aimed to identify IA susceptibility genes in the Portuguese population through a pool-based multistage genome-wide association study. Replicate pools were allelotyped in triplicate in a discovery dataset (100 IA cases and 92 gender-matched controls) using the Affymetrix Human SNP Array 6.0. Top SNPs (absolute value of the relative allele score difference between cases and controls |RASdiff|≥13.0%) were selected for technical validation by individual genotyping in the discovery dataset. From the 101 SNPs successfully genotyped, 99 SNPs were nominally associated with IA. Replication of technically validated SNPs was conducted in an independent replication dataset (100 Portuguese IA cases and 407 controls). rs4667622 (between UBR3 and MYO3B), rs6599001 (between SCN11A and WDR48), rs3932338 (214 kilobases downstream of PRDM9), and rs10943471 (96 kilobases upstream of HTR1B) were associated with IA (unadjusted allelic chi-square tests) in the datasets tested (discovery: 6.84E-04≤P≤1.92E-02, replication: 2.66E-04≤P≤2.28E-02, and combined datasets: 6.05E-05≤P≤5.50E-04). Additionally, we confirmed the known association with IA of rs1333040 at the 9p21.3 genomic region, thus validating our dataset. These novel findings in the Portuguese population warrant further replication in additional independent studies, and provide additional candidates to more comprehensively understand IA etiopathogenesis.pt_PT
dc.description.sponsorshipFCT grant: (CMUP-ERI/TPE/0028/2013), FCT fellowships and research contracts (SFRH/BPD/35737/2007, SFRH/BPD/70008/2010, SFRH/BD/43895/2008 and Ciência and Investigator- FCT contracts).pt_PT
dc.identifier10.1371/journal.pone.0133422
dc.identifier.citationAbrantes P, Santos MM, Sousa I, Xavier JM, Francisco V, Krug T, et al. (2015) Genetic Variants Underlying Risk of Intracranial Aneurysms: Insights from a GWAS in Portugal. PLoS ONE 10(7): e0133422. doi:10.1371/journal.pone.0133422pt_PT
dc.identifier.doi10.1371/journal.pone.0133422
dc.identifier.urihttp://hdl.handle.net/10400.7/407
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationPatients as Health Care Innovators: An Empirical Investigation of Treatment, Therapies and Medical Devices (TT&MD) developed by Patients of Chronic Diseases
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133422pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectIntracranial Aneurysmpt_PT
dc.subjectGeneticpt_PT
dc.titleGenetic Variants Underlying Risk of Intracranial Aneurysms: Insights from a GWAS in Portugalpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePatients as Health Care Innovators: An Empirical Investigation of Treatment, Therapies and Medical Devices (TT&MD) developed by Patients of Chronic Diseases
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-GMG%2F101537%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FIIM-GES%2F5015%2F2012/PT
oaire.citation.endPage12pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLOS Onept_PT
oaire.citation.volume10pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicatione1b4d661-ee31-4497-9466-9750fd80dd48
relation.isProjectOfPublication0206096c-bb4f-47b7-a19e-5b5e08948e64
relation.isProjectOfPublication.latestForDiscoverye1b4d661-ee31-4497-9466-9750fd80dd48

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