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Article: A joint study of whole exome sequencing and structural MRI analysis in major depressive disorder

TitleA joint study of whole exome sequencing and structural MRI analysis in major depressive disorder
Authors
KeywordsMRI
Major depressive disorder
parallel ICA
whole exome sequencing
Issue Date2019
PublisherCambridge University Press. The Journal's web site is located at http://journals.cambridge.org/action/displayJournal?jid=PSM
Citation
Psychological Medicine, 2019, Epub, p. 1-12 How to Cite?
AbstractBackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide and influenced by both environmental and genetic factors. Genetic studies of MDD have focused on common variants and have been constrained by the heterogeneity of clinical symptoms.MethodsWe sequenced the exome of 77 cases and 245 controls of Han Chinese ancestry and scanned their brain. Burden tests of rare variants were performed first to explore the association between genes/pathways and MDD. Secondly, parallel Independent Component Analysis was conducted to investigate genetic underpinnings of gray matter volume (GMV) changes of MDD.ResultsTwo genes (CSMD1, p = 5.32×10-6; CNTNAP5, p = 1.32×10-6) and one pathway (Neuroactive Ligand Receptor Interactive, p = 1.29×10-5) achieved significance in burden test. In addition, we identified one pair of imaging-genetic components of significant correlation (r = 0.38, p = 9.92×10-6). The imaging component reflected decreased GMV in cases and correlated with intelligence quotient (IQ). IQ mediated the effects of GMV on MDD. The genetic component enriched in two gene sets, namely Singling by G-protein coupled receptors [false discovery rate (FDR) q = 3.23×10-4) and Alzheimer Disease Up (FDR q = 6.12×10-4).ConclusionsBoth rare variants analysis and imaging-genetic analysis found evidence corresponding with the neuroinflammation and synaptic plasticity hypotheses of MDD. The mediation of IQ indicates that genetic component may act on MDD through GMV alteration and cognitive impairment. Copyright © Cambridge University Press 2019.
Persistent Identifierhttp://hdl.handle.net/10722/274014
ISSN
2019 Impact Factor: 5.813
2015 SCImago Journal Rankings: 2.843

 

DC FieldValueLanguage
dc.contributor.authorZhang, Y-
dc.contributor.authorLi, M-
dc.contributor.authorWang, Q-
dc.contributor.authorHsu, JS-
dc.contributor.authorDeng, W-
dc.contributor.authorMa, X-
dc.contributor.authorNi, P-
dc.contributor.authorZhao, L-
dc.contributor.authorTian, Y-
dc.contributor.authorSham, PC-
dc.contributor.authorLi, T-
dc.date.accessioned2019-08-18T14:53:18Z-
dc.date.available2019-08-18T14:53:18Z-
dc.date.issued2019-
dc.identifier.citationPsychological Medicine, 2019, Epub, p. 1-12-
dc.identifier.issn0033-2917-
dc.identifier.urihttp://hdl.handle.net/10722/274014-
dc.description.abstractBackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide and influenced by both environmental and genetic factors. Genetic studies of MDD have focused on common variants and have been constrained by the heterogeneity of clinical symptoms.MethodsWe sequenced the exome of 77 cases and 245 controls of Han Chinese ancestry and scanned their brain. Burden tests of rare variants were performed first to explore the association between genes/pathways and MDD. Secondly, parallel Independent Component Analysis was conducted to investigate genetic underpinnings of gray matter volume (GMV) changes of MDD.ResultsTwo genes (CSMD1, p = 5.32×10-6; CNTNAP5, p = 1.32×10-6) and one pathway (Neuroactive Ligand Receptor Interactive, p = 1.29×10-5) achieved significance in burden test. In addition, we identified one pair of imaging-genetic components of significant correlation (r = 0.38, p = 9.92×10-6). The imaging component reflected decreased GMV in cases and correlated with intelligence quotient (IQ). IQ mediated the effects of GMV on MDD. The genetic component enriched in two gene sets, namely Singling by G-protein coupled receptors [false discovery rate (FDR) q = 3.23×10-4) and Alzheimer Disease Up (FDR q = 6.12×10-4).ConclusionsBoth rare variants analysis and imaging-genetic analysis found evidence corresponding with the neuroinflammation and synaptic plasticity hypotheses of MDD. The mediation of IQ indicates that genetic component may act on MDD through GMV alteration and cognitive impairment. Copyright © Cambridge University Press 2019.-
dc.languageeng-
dc.publisherCambridge University Press. The Journal's web site is located at http://journals.cambridge.org/action/displayJournal?jid=PSM-
dc.relation.ispartofPsychological Medicine-
dc.rightsPsychological Medicine. Copyright © Cambridge University Press.-
dc.rightsThis article has been published in a revised form in [Journal] [http://doi.org/XXX]. This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. © copyright holder.-
dc.subjectMRI-
dc.subjectMajor depressive disorder-
dc.subjectparallel ICA-
dc.subjectwhole exome sequencing-
dc.titleA joint study of whole exome sequencing and structural MRI analysis in major depressive disorder-
dc.typeArticle-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.authoritySham, PC=rp00459-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1017/S0033291719000072-
dc.identifier.pmid30722798-
dc.identifier.scopuseid_2-s2.0-85061162091-
dc.identifier.hkuros300985-
dc.identifier.spage1-
dc.identifier.epage12-
dc.publisher.placeUnited Kingdom-

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