Sex differences in the genetic architecture of obsessive-compulsive disorder

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorKHRAMTSOVA, Ekaterina A.
dc.contributor.authorHELDMAN, Raphael
dc.contributor.authorDERKS, Eske M.
dc.contributor.authorYU, Dongmei
dc.contributor.authorDAVIS, Lea K.
dc.contributor.authorSTRANGER, Barbara E.
dc.contributor.authorARNOLD, Paul D.
dc.contributor.authorASKLAND, Kathleen D.
dc.contributor.authorBARLASSINA, Cristina
dc.contributor.authorBELLODI, Laura
dc.contributor.authorBIENVENU, O. J.
dc.contributor.authorBLACK, Donald
dc.contributor.authorBLOCH, Michael
dc.contributor.authorBRENTANI, Helena
dc.contributor.authorBURTON, Christie L.
dc.contributor.authorCAMARENA, Beatriz
dc.contributor.authorCAPPI, Carolina
dc.contributor.authorCATH, Danielle
dc.contributor.authorCAVALLINI, Maria
dc.contributor.authorCONTI, David
dc.contributor.authorCOOK, Edwin
dc.contributor.authorCORIC, Vladimir
dc.contributor.authorCULLEN, Bernadette A.
dc.contributor.authorCUSI, Danielle
dc.contributor.authorDAVIS, Lea K.
dc.contributor.authorDELORME, Richard
dc.contributor.authorDENYS, Damiaan
dc.contributor.authorDERKS, Eske
dc.contributor.authorEAPEN, Valsamma
dc.contributor.authorEDLUND, Christopher
dc.contributor.authorERDMAN, Lauren
dc.contributor.authorFALKAI, Peter
dc.contributor.authorFIGEE, Martijn
dc.contributor.authorFYER, Abigail J.
dc.contributor.authorGELLER, Daniel A.
dc.contributor.authorGOES, Fernando S.
dc.contributor.authorGRABE, Hans
dc.contributor.authorGRADOS, Marcos A.
dc.contributor.authorGREENBERG, Benjamin D.
dc.contributor.authorGRUNBLATT, Edna
dc.contributor.authorGUO, Wei
dc.contributor.authorHANNA, Gregory L.
dc.contributor.authorHEMMINGS, Sian
dc.contributor.authorHOUNIE, Ana G.
dc.contributor.authorJENICKE, Michael
dc.contributor.authorKEENAN, Clare
dc.contributor.authorKENNEDY, James
dc.contributor.authorKHRAMTSOVA, Ekaterina A.
dc.contributor.authorKONKASHBAEV, Anuar
dc.contributor.authorKNOWLES, James A.
dc.contributor.authorKRASNOW, Janice
dc.contributor.authorLANGE, Cristophe
dc.contributor.authorLANZAGORTA, Nuria
dc.contributor.authorLEBOYER, Marion
dc.contributor.authorLENNERTZ, Leonhard
dc.contributor.authorLI, Bingbin
dc.contributor.authorLIANG, K-Y
dc.contributor.authorLOCHNER, Christine
dc.contributor.authorMACCIARDI, Fabio
dc.contributor.authorMAHER, Brion
dc.contributor.authorMAIER, Wolfgang
dc.contributor.authorMARCONI, Maurizio
dc.contributor.authorMATHEWS, Carol A.
dc.contributor.authorMATTHESIEN, Manuel
dc.contributor.authorMCCRACKEN, James T.
dc.contributor.authorMCLAUGHLIN, Nicole C.
dc.contributor.authorMIGUEL, Euripedes C.
dc.contributor.authorMOESSNER, Rainald
dc.contributor.authorMURPHY, Dennis L.
dc.contributor.authorNEALE, Benjamin
dc.contributor.authorNESTADT, Gerald
dc.contributor.authorNESTADT, Paul
dc.contributor.authorNICOLINI, Humberto
dc.contributor.authorNURMI, Ericka
dc.contributor.authorOSIECKI, Lisa
dc.contributor.authorPATO, Carlos
dc.contributor.authorPATO, Michelle
dc.contributor.authorPAULS, David L.
dc.contributor.authorPIACENTINI, John
dc.contributor.authorPOSTHUMA, Danielle
dc.contributor.authorPULVER, Ann E.
dc.contributor.authorQIN, H-D
dc.contributor.authorRASMUSSEN, Steven A.
dc.contributor.authorRAUCH, Scott
dc.contributor.authorRICHTER, Margaret A.
dc.contributor.authorRIDDLE, Mark A.
dc.contributor.authorRIPKE, Stephan
dc.contributor.authorRUHRMANN, Stephan
dc.contributor.authorSAMPAIO, Aline S.
dc.contributor.authorSAMUELS, Jack F.
dc.contributor.authorSCHARF, Jeremiah M.
dc.contributor.authorSHUGART, Yin Yao
dc.contributor.authorSMIT, Jan
dc.contributor.authorSTEIN, Daniel
dc.contributor.authorSTEWART, S. Evelyn
dc.contributor.authorTURIEL, Maurizio
dc.contributor.authorVALLADA, Homero
dc.contributor.authorVEENSTRA-VANDERWEELE, Jeremy
dc.contributor.authorWAGNER, Michael
dc.contributor.authorWALITZA, Susanne
dc.contributor.authorWANG, Y.
dc.contributor.authorWENDLAND, Jens
dc.contributor.authorVULINK, Nienke
dc.contributor.authorYU, Dongmei
dc.contributor.authorZAI, Gwyneth
dc.contributor.groupauthorTourette Syndrome Obsessive
dc.date.accessioned2019-09-23T14:20:14Z
dc.date.available2019-09-23T14:20:14Z
dc.date.issued2019
dc.description.abstractObsessive-compulsive disorder (OCD) is a highly heritable complex phenotype that demonstrates sex differences in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome-wide characterization of the sex-specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sex differences including a sex-dependent liability threshold, the presence of individual sex-specific risk variants on the autosomes and the X chromosome, and sex-specific pleiotropic effects. Furthermore, we tested the hypothesis that genetic heterogeneity between the sexes may obscure associations in a sex-combined genome-wide association study. We observed a strong genetic correlation between male and female OCD and no evidence for a sex-dependent liability threshold model, suggesting that sex-combined analysis does not suffer from widespread loss of power because of genetic heterogeneity between the sexes. While we did not detect any significant sex-specific genome-wide single nucleotide polymorphisms (SNP) associations, we did identify two significant gene-based associations in females: GRID2 and GRP135, which showed no association in males. We observed that the SNPs with sexually differentiated effects showed an enrichment of regulatory variants influencing expression of genes in brain and immune tissues. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex-specific genetic risk factors for OCD.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipDavid Judah Foundation [MH087748, MH085057, S40024, MH073250, MH079489]
dc.description.sponsorshipNational Institute of Mental Health [MH002930-06, MH071507, MH079487, MH079488, MH079494]
dc.description.sponsorshipNational Institutes of Health [3P50MH094267-04S1, UL1 TR000430, 5U01MH109528-03]
dc.identifier.citationAMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, v.180, n.6, Special Issue, p.351-364, 2019
dc.identifier.doi10.1002/ajmg.b.32687
dc.identifier.eissn1552-485X
dc.identifier.issn1552-4841
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/33554
dc.language.isoeng
dc.publisherWILEYeng
dc.relation.ispartofAmerican Journal of Medical Genetics Part B-Neuropsychiatric Genetics
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright WILEYeng
dc.subjectgeneticseng
dc.subjectgenome-wide association studyeng
dc.subjectobsessive compulsive disordereng
dc.subjectsex differenceseng
dc.subjectsex-specific analysiseng
dc.subjectsex-specific genetic architectureeng
dc.subject.othergenome-wide associationeng
dc.subject.othertourette-syndromeeng
dc.subject.otherriskeng
dc.subject.othermetaanalysiseng
dc.subject.otherautoimmuneeng
dc.subject.otherchildreneng
dc.subject.otherdiseaseeng
dc.subject.otherepidemiologyeng
dc.subject.otherneurobiologyeng
dc.subject.otherinsightseng
dc.subject.wosGenetics & Heredityeng
dc.subject.wosPsychiatryeng
dc.titleSex differences in the genetic architecture of obsessive-compulsive disordereng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryAustrália
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisoau
hcfmusp.author.externalKHRAMTSOVA, Ekaterina A.:Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA; Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA
hcfmusp.author.externalHELDMAN, Raphael:Univ Calif Berkeley, Berkeley, CA 94720 USA
hcfmusp.author.externalDERKS, Eske M.:Queensland Inst Med Res, Brisbane, Qld, Australia
hcfmusp.author.externalYU, Dongmei:Harvard Med Sch, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Genom Med,Dept Psychiat, Boston, MA 02115 USA
hcfmusp.author.externalDAVIS, Lea K.:Vanderbilt Genet Inst, Nashville, TN 37235 USA; Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA; Vanderbilt Univ, Med Ctr, Dept Med, Div Med Genet, Nashville, TN USA; Vanderbilt Univ, Med Ctr, Dept Psychiat & Behav Sci, Nashville, TN USA
hcfmusp.author.externalSTRANGER, Barbara E.:Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA; Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA; Univ Chicago, Ctr Data Intens Sci, Chicago, IL 60637 USA
hcfmusp.author.externalDAVIS, Lea K.:Vanderbilt Genet Inst, Nashville, TN 37235 USA; Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA; Vanderbilt Univ, Med Ctr, Dept Med, Div Med Genet, Nashville, TN USA; Vanderbilt Univ, Med Ctr, Dept Psychiat & Behav Sci, Nashville, TN USA
hcfmusp.author.externalDERKS, Eske:Queensland Inst Med Res, Brisbane, Qld, Australia
hcfmusp.author.externalKHRAMTSOVA, Ekaterina A.:Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA; Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA
hcfmusp.author.externalYU, Dongmei:Harvard Med Sch, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Genom Med,Dept Psychiat, Boston, MA 02115 USA
hcfmusp.citation.scopus38
hcfmusp.contributor.author-fmusphcHELENA PAULA BRENTANI
hcfmusp.contributor.author-fmusphcCAROLINA CAPPI
hcfmusp.contributor.author-fmusphcANA GABRIELA HOUNIE
hcfmusp.contributor.author-fmusphcEURIPEDES CONSTANTINO MIGUEL FILHO
hcfmusp.contributor.author-fmusphcDANIELE MONTORO STEIN
hcfmusp.contributor.author-fmusphcHOMERO PINTO VALLADA FILHO
hcfmusp.description.beginpage351
hcfmusp.description.endpage364
hcfmusp.description.issue6
hcfmusp.description.issueSpecial Issue
hcfmusp.description.volume180
hcfmusp.origemWOS
hcfmusp.origem.pubmed30456828
hcfmusp.origem.scopus2-s2.0-85056780623
hcfmusp.origem.wosWOS:000478086300004
hcfmusp.publisher.cityHOBOKENeng
hcfmusp.publisher.countryUSAeng
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