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Association of a Schizophrenia-Risk Nonsynonymous Variant With Putamen Volume in Adolescents: A Voxelwise and Genome-Wide Association Study

dc.rights.licenseopenen_US
dc.contributor.authorLUO, Q.
dc.contributor.authorCHEN, Q.
dc.contributor.authorWANG, W.
dc.contributor.authorDESRIVIERES, S.
dc.contributor.authorQUINLAN, E. B.
dc.contributor.authorJIA, T.
dc.contributor.authorMACARE, C.
dc.contributor.authorROBERT, G. H.
dc.contributor.authorCUI, J.
dc.contributor.authorGUEDJ, M.
dc.contributor.authorPALANIYAPPAN, L.
dc.contributor.authorKHERIF, F.
dc.contributor.authorBANASCHEWSKI, T.
dc.contributor.authorBOKDE, A. L. W.
dc.contributor.authorBUCHEL, C.
dc.contributor.authorFLOR, H.
dc.contributor.authorFROUIN, V.
dc.contributor.authorGARAVAN, H.
dc.contributor.authorGOWLAND, P.
dc.contributor.authorHEINZ, A.
dc.contributor.authorITTERMANN, B.
dc.contributor.authorMARTINOT, J. L.
dc.contributor.authorARTIGES, E.
dc.contributor.authorPAILLERE-MARTINOT, M. L.
dc.contributor.authorNEES, F.
dc.contributor.authorORFANOS, D. P.
dc.contributor.authorPOUSTKA, L.
dc.contributor.authorFROHNER, J. H.
dc.contributor.authorSMOLKA, M. N.
dc.contributor.authorWALTER, H.
dc.contributor.authorWHELAN, R.
dc.contributor.authorCALLICOTT, J. H.
dc.contributor.authorMATTAY, V. S.
dc.contributor.authorPAUSOVA, Z.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDARTIGUES, Jean-Francois
ORCID: 0000-0001-9482-5529
IDREF: 058586105
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorCRIVELLO, F.
dc.contributor.authorBERMAN, K. F.
dc.contributor.authorLI, F.
dc.contributor.authorPAUS, T.
dc.contributor.authorWEINBERGER, D. R.
dc.contributor.authorMURRAY, R. M.
dc.contributor.authorSCHUMANN, G.
dc.contributor.authorFENG, J.
dc.date.accessioned2020-06-29T06:58:29Z
dc.date.available2020-06-29T06:58:29Z
dc.date.issued2019-01-16
dc.identifier.issn2168-6238 (Electronic) 2168-622X (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/8248
dc.description.abstractEnImportance: Deviation from normal adolescent brain development precedes manifestations of many major psychiatric symptoms. Such altered developmental trajectories in adolescents may be linked to genetic risk for psychopathology. Objective: To identify genetic variants associated with adolescent brain structure and explore psychopathologic relevance of such associations. Design, Setting, and Participants: Voxelwise genome-wide association study in a cohort of healthy adolescents aged 14 years and validation of the findings using 4 independent samples across the life span with allele-specific expression analysis of top hits. Group comparison of the identified gene-brain association among patients with schizophrenia, unaffected siblings, and healthy control individuals. This was a population-based, multicenter study combined with a clinical sample that included participants from the IMAGEN cohort, Saguenay Youth Study, Three-City Study, and Lieber Institute for Brain Development sample cohorts and UK biobank who were assessed for both brain imaging and genetic sequencing. Clinical samples included patients with schizophrenia and unaffected siblings of patients from the Lieber Institute for Brain Development study. Data were analyzed between October 2015 and April 2018. Main Outcomes and Measures: Gray matter volume was assessed by neuroimaging and genetic variants were genotyped by Illumina BeadChip. Results: The discovery sample included 1721 adolescents (873 girls [50.7%]), with a mean (SD) age of 14.44 (0.41) years. The replication samples consisted of 8690 healthy adults (4497 women [51.8%]) from 4 independent studies across the life span. A nonsynonymous genetic variant (minor T allele of rs13107325 in SLC39A8, a gene implicated in schizophrenia) was associated with greater gray matter volume of the putamen (variance explained of 4.21% in the left hemisphere; 8.66; 95% CI, 6.59-10.81; P = 5.35 x 10-18; and 4.44% in the right hemisphere; t = 8.90; 95% CI, 6.75-11.19; P = 6.80 x 10-19) and also with a lower gene expression of SLC39A8 specifically in the putamen (t127 = -3.87; P = 1.70 x 10-4). The identified association was validated in samples across the life span but was significantly weakened in both patients with schizophrenia (z = -3.05; P = .002; n = 157) and unaffected siblings (z = -2.08; P = .04; n = 149). Conclusions and Relevance: Our results show that a missense mutation in gene SLC39A8 is associated with larger gray matter volume in the putamen and that this association is significantly weakened in schizophrenia. These results may suggest a role for aberrant ion transport in the etiology of psychosis and provide a target for preemptive developmental interventions aimed at restoring the functional effect of this mutation.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subject.enHEALTHY
dc.subject.enSEPIA
dc.subject.enFR
dc.title.enAssociation of a Schizophrenia-Risk Nonsynonymous Variant With Putamen Volume in Adolescents: A Voxelwise and Genome-Wide Association Study
dc.title.alternativeJAMA Psychiatryen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1001/jamapsychiatry.2018.4126en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30649180en_US
bordeaux.journalJAMA psychiatryen_US
bordeaux.page435-445en_US
bordeaux.volume76en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue4en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamSEPIA
bordeaux.teamHEALTHY_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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