{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:13:06Z","timestamp":1791468786231,"version":"4.3.4"},"reference-count":91,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH002930\u201006 MH071507 MH079487 MH079488 MH079489 MH079494"],"award-info":[{"award-number":["MH002930\u201006 MH071507 MH079487 MH079488 MH079489 MH079494"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3P50MH094267\u201004S1MH073250MH079489 MH085057MH087748S40024UL1 TR000430"],"award-info":[{"award-number":["3P50MH094267\u201004S1MH073250MH079489 MH085057MH087748S40024UL1 TR000430"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH079494"],"award-info":[{"award-number":["MH079494"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH079488"],"award-info":[{"award-number":["MH079488"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH079487"],"award-info":[{"award-number":["MH079487"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH079489"],"award-info":[{"award-number":["MH079489"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH071507"],"award-info":[{"award-number":["MH071507"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Obsessive\u2013compulsive 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\u2010wide characterization of the sex\u2010specific 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\u2010dependent liability threshold, the presence of individual sex\u2010specific risk variants on the autosomes and the X chromosome, and sex\u2010specific pleiotropic effects. Furthermore, we tested the hypothesis that genetic heterogeneity between the sexes may obscure associations in a sex\u2010combined genome\u2010wide association study. We observed a strong genetic correlation between male and female OCD and no evidence for a sex\u2010dependent liability threshold model, suggesting that sex\u2010combined analysis does not suffer from widespread loss of power because of genetic heterogeneity between the sexes. While we did not detect any significant sex\u2010specific genome\u2010wide single nucleotide polymorphisms (SNP) associations, we did identify two significant gene\u2010based 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\u2010specific genetic risk factors for OCD.<\/jats:p>","DOI":"10.1002\/ajmg.b.32687","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T04:25:57Z","timestamp":1542687957000},"page":"351-364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Sex differences in the genetic architecture of obsessive\u2013compulsive disorder"],"prefix":"10.1002","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-454X","authenticated-orcid":false,"given":"Ekaterina A.","family":"Khramtsova","sequence":"first","affiliation":[{"name":"Section of Genetic Medicine, Department of Medicine University of Chicago  Chicago Illinois"},{"name":"Institute for Genomics and Systems Biology, University of Chicago  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Heldman","sequence":"additional","affiliation":[{"name":"University of California  Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eske M.","family":"Derks","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Yu","sequence":"additional","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry Harvard Medical School, Massachusetts General Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Tourette Syndrome\/Obsessive\u2010Compulsive Disorder Working Group of the Psychiatric Genomics Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea K.","family":"Davis","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute; Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Division of Medical Genetics, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara E.","family":"Stranger","sequence":"additional","affiliation":[{"name":"Section of Genetic Medicine, Department of Medicine University of Chicago  Chicago Illinois"},{"name":"Institute for Genomics and Systems Biology, University of Chicago  Chicago Illinois"},{"name":"Center for Data Intensive Science University of Chicago  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4398"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3698"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(92)90075-E"},{"issue":"4","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.31887\/DCNS.2011.13.4\/bboileau","article-title":"A review of obsessive\u2013compulsive disorder in children and adolescents","volume":"13","author":"Boileau B.","year":"2011","journal-title":"Dialogues in Clinical Neuroscience"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.187"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap8757"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2307\/2529826"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3406"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3211"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.30"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.80.4.353"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.153"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003864"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2307"},{"issue":"2","key":"e_1_2_9_16_1","article-title":"Obsessive\u2013compulsive symptoms in a large population\u2010based twin\u2010family sample are predicted by clinically based polygenic scores and by genome\u2010wide SNPs","volume":"6","author":"Braber A.","year":"2016","journal-title":"Translational Psychiatry"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","unstructured":"Duncan L. E. A.Ratanatharathorn A. E.Aiello L. M.Almli A. B.Amstadter A. E.Ashley\u2010Koch D. G.Baker J. C.Beckham L. J.Bierut J.Bisson B.Bradley C.Y.Chen S.Dalvie L. A.Farrer S.Galea M. E.Garrett J. E.Gelernter G.Guffanti M. A.Hauser E. O.Johnson R. C.Kessler N. A.Kimbrel A.King N.Koen H. R.Kranzler M. W.Logue A. X.Maihofer A. R.Martin M. W.Miller R. A.Morey N. R.Nugent J. P.Rice S.Ripke A. L.Roberts N. L.Saccone J. W.Smoller D. J.Stein M. B.Stein J. A.Sumner M.Uddin R. J.Ursano D. E.Wildman R.Yehuda H.Zhao M. J.Daly I.Liberzon K. J.Ressler C. M.Nievergelt K. C.Koenen2017.Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.Molecular Psychiatry.https:\/\/doi.org\/10.1038\/mp.2017.77.","DOI":"10.1038\/mp.2017.77"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.1990.tb01575.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2015.06.009"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2015.05.036"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esv059"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00113-6"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1375\/twin.8.5.450"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24277"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3888"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.04.014"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10558"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3102"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13624"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14101"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spl.2004.11.028"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.111.001198"},{"key":"e_1_2_9_33_1","first-page":"1181","article-title":"Revealing the complex genetic architecture of obsessive\u2013compulsive disorder using meta\u2010analysis","volume":"23","author":"International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF\u2010GC) and OCD Collaborative Genetics Association Studies (OCGAS)","year":"2017","journal-title":"Molecular Psychiatry"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000225070.13682.11"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.06.012"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.617"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","unstructured":"Khramtsova Ekaterina A. andBarbara E.Stranger.2016.Assocplots: A python package for static and interactive visualization of multiple\u2010group GWAS results.Bioinformatics.https:\/\/doi.org\/10.1093\/bioinformatics\/btw641.","DOI":"10.1101\/062737"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2014.96"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.K.01450"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"e_1_2_9_42_1","first-page":"83","article-title":"Tourette syndrome and obsessive\u2013compulsive disorder","volume":"58","author":"Leonard H. L.","year":"1992","journal-title":"Advances in Neurology"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1081-y"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(03)00063-4"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14177"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.21"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(98)00371-0"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525466113"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.11.026"},{"key":"e_1_2_9_50_1","doi-asserted-by":"crossref","unstructured":"Martin J. Walters R. K. Demontis D. Mattheisen M. Lee S. H. Robinson E. \u2026 Neale B. M.2017.A genetic investigation of sex bias in the prevalence of attention deficit hyperactivity disorder.bioRxiv.https:\/\/doi.org\/10.1101\/154088.","DOI":"10.1101\/154088"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1516-44462011000400014"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.43"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.7.4.507"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006425"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2006.02.003"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.07.012"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2010.06.008"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.4.358"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2009.11.001"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3552"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17671"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys104"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.11"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu655"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.09.006"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.943"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu516"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1249547"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003500"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.94"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.69"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13595"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611243113"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000005300"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v65n0303"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001542"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.85"},{"key":"e_1_2_9_80_1","unstructured":"Swedo S. E. J. F.Leckman N. R. Rose \u2013 Pediatr Therapeut and2012From research subgroup to clinical syndrome: Modifying the PANDAS criteria to describe PANS (pediatric acute\u2010onset neuropsychiatric syndrome).Kids.iocdf.org.https:\/\/kids.iocdf.org\/wp-content\/uploads\/sites\/6\/2015\/07\/PANDAS-to-PANS-Final-form-for-Pediatrics-Therapeutics-2012.pdf"},{"issue":"2","key":"e_1_2_9_81_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1176\/ajp.155.2.264","article-title":"Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases","volume":"155","author":"Swedo S. E.","year":"1998","journal-title":"The American Journal of Psychiatry"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1989.01810040041007"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-14-33"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.571"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1516-44462005000300015"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"e_1_2_9_87_1","first-page":"5","article-title":"The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group","volume":"55","author":"Weissman M. M.","year":"1994","journal-title":"The Journal of Clinical Psychiatry"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005378"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.011"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2014.13101306"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/1753-6561-3-s7-s90"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.b.32687","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.32687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T21:27:06Z","timestamp":1694294826000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.32687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,20]]},"references-count":91,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/ajmg.b.32687"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.32687","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/219170","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.734474012.793580415","asserted-by":"object"}]},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"value":"1552-4841","type":"print"},{"value":"1552-485X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,20]]},"assertion":[{"value":"2018-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}