{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:31:59Z","timestamp":1783960319612,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acamh.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Child Psychology Psychiatry"],"published-print":{"date-parts":[[2019,12]]},"abstract":"\n Background<\/jats:title>\n \n Serotonin system genes are commonly studied in obsessive\u2010compulsive disorder (\n OCD<\/jats:styled-content>\n ), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive\u2010compulsive (\n OC<\/jats:styled-content>\n ) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different\n OC<\/jats:styled-content>\n trait dimensions and, furthermore, that they vary by sex.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Obsessive\u2010compulsive trait dimensions (Cleaning\/Contamination, Counting\/Checking, Symmetry\/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive\u2010Compulsive Scale (\n TOCS<\/jats:styled-content>\n ). We genotyped candidate serotonin genes (directly genotyping the\n \n 5\u2010\n HTTLPR<\/jats:styled-content>\n <\/jats:italic>\n polymorphism in\n \n SLC<\/jats:styled-content>\n 6A4\n <\/jats:italic>\n for 2018 individuals and using single nucleotide polymorphism (\n SNP<\/jats:styled-content>\n ) array data for genes\n \n SLC<\/jats:styled-content>\n 6A4\n <\/jats:italic>\n ,\n \n HTR<\/jats:styled-content>\n 2A\n <\/jats:italic>\n , and\n \n HTR<\/jats:styled-content>\n 1B\n <\/jats:italic>\n for 4711 individuals). We assessed the association between variants across these genes and each of the\n OC<\/jats:styled-content>\n trait dimensions, within males and females separately. We analyzed\n OC<\/jats:styled-content>\n traits as both (a) dichotomized based on a threshold value and (b) quantitative scores.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The [\n \n L\n G<\/jats:sub>\n <\/jats:styled-content>\n + S] variant in\n \n 5\u2010\n HTTLPR<\/jats:styled-content>\n <\/jats:italic>\n was significantly associated with hoarding in males (\n p<\/jats:italic>\n \u2010value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for\n \n 5\u2010\n HTTLPR<\/jats:styled-content>\n <\/jats:italic>\n in females. Using\n SNP<\/jats:styled-content>\n array data, there were significant findings for rumination in males for\n \n HTR<\/jats:styled-content>\n 2A\n <\/jats:italic>\n SNP<\/jats:styled-content>\n s (\n p<\/jats:italic>\n \u2010value of 1.04e\u20106 to 5.20e\u20106).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This represents the first genetic association study of\n OC<\/jats:styled-content>\n trait dimensions in a community\u2010based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in\n OCD<\/jats:styled-content>\n should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jcpp.13079","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T04:47:44Z","timestamp":1563511664000},"page":"1289-1299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Serotonin system genes and obsessive\u2010compulsive trait dimensions in a population\u2010based, pediatric sample: a genetic association study"],"prefix":"10.1111","volume":"60","author":[{"given":"Vanessa M.","family":"Sinopoli","sequence":"first","affiliation":[{"name":"Institute of Medical Science University of Toronto Toronto ON Canada"},{"name":"Program in Genetics & Genome Biology The Hospital for Sick Children Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Erdman","sequence":"additional","affiliation":[{"name":"Program in Genetics & Genome Biology The Hospital for Sick Children Toronto ON Canada"},{"name":"Department of Computer Science University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie L.","family":"Burton","sequence":"additional","affiliation":[{"name":"Program in Genetics & Genome Biology The Hospital for Sick Children Toronto ON Canada"},{"name":"Program in Neurosciences and Mental Health The Hospital for Sick Children Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura S.","family":"Park","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto Toronto ON Canada"},{"name":"Program in Genetics & Genome Biology The Hospital for Sick Children Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Clinical Research Services The Hospital for Sick Children Toronto ON Canada"},{"name":"Dalla Lana School of Public Health University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Shan","sequence":"additional","affiliation":[{"name":"Program in Neurosciences and Mental Health The Hospital for Sick Children Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Goodale","sequence":"additional","affiliation":[{"name":"Program in Neurosciences and Mental Health The Hospital for Sick Children Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.\u2010M.","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Mathison Centre for Mental Health Research & Education Hotchkiss Brain Institute University of Calgary Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Crosbie","sequence":"additional","affiliation":[{"name":"Program in Neurosciences and Mental Health The Hospital for Sick Children Toronto ON Canada"},{"name":"Department of Psychiatry University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell J.","family":"Schachar","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto Toronto ON Canada"},{"name":"Program in Neurosciences and Mental Health The Hospital for Sick Children Toronto ON Canada"},{"name":"Department of Psychiatry University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Program in Genetics & Genome Biology The Hospital for Sick Children Toronto ON Canada"},{"name":"Mathison Centre for Mental Health Research & Education Hotchkiss Brain Institute University of Calgary Calgary AB Canada"},{"name":"Departments of Psychiatry and Medical Genetics Cumming School of Medicine University of Calgary Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.110109"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2015.01.018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-004-0459-4"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000257"},{"key":"e_1_2_8_7_1","first-page":"14","article-title":"A role for the serotonin system in the mechanism of action of antidepressant treatments: Preclinical evidence","volume":"51","author":"Blier 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Crosbie J. Erdman L. Dupuis A. Park L.S. Sinopoli V. \u2026 &Arnold P.D.. (2015)A hypothesis\u2010driven genome\u2010wide association study of an obsessive\u2010compulsive quantitative trait in a community\u2010based sample of children and adolescents. Oral talk at the\u00a023nd\u00a0World Congress of Psychiatric Genetics Meeting October\u00a02015 Toronto ON."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0249-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1700"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10802-012-9693-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4934"},{"key":"e_1_2_8_15_1","unstructured":"Flament M.(1990).Epidemiology of obsessive\u2010compulsive disorder in children and adolescents. 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