Serotonin system genes and hoarding with and without other obsessive–compulsive traits in a population‐based, pediatric sample: A genetic association study

Background Hoarding, originally only considered a symptom of obsessive‐compulsive disorder (OCD), is now categorized as a separate disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). We studied candidate serotonergic genes and the distinctness of hoarding in children and adolescents and hypothesized that unique gene variants would be associated with hoarding alone. Methods We examined obsessive–compulsive (OC) traits, including hoarding, in a total of 5,213 pediatric participants in the community. We genotyped candidate serotonin genes (5‐HTTLPR polymorphism in SLC6A4 for 2,018 individuals and single nucleotide polymorphisms [SNPs] across genes SLC6A4, HTR2A, and HTR1B for 4,711 individuals). In a previous study conducted by our group in the same sample, we identified a significant association between 5‐HTTLPR and hoarding in males. In this study, we examined hoarding more closely by testing the association between serotonin gene variants and hoarding traits with and without other accompanying OC traits. Results The [LG+S] variant in 5‐HTTLPR was significantly associated with hoarding alone in males (p‐value of 0.009). There were no significant findings for 5‐HTTLPR in females. There were no significant findings after correction for multiple comparisons using SNP array data, but top SNP findings suggested that variation downstream of HTR1B may be implicated in hoarding alone in females. Conclusions Our results suggest specific serotonin gene variants are associated with hoarding traits alone, differing between sexes. Top findings are in line with our former study, suggesting that individuals with hoarding alone were driving previous results. Our paper supports hoarding disorder's new designation. Key points Hoarding often presents independently from OCD and is biologically distinct 5‐HTTLPR variant [LG+S] is significantly associated with hoarding without other OC symptoms in pediatric males in the community Our top SNP findings suggest that variation downstream of HTR1B may also be implicated in hoarding alone in females Hoarding without other OCD symptoms may have distinct underlying serotonin system genetics and the associated variation may depend on sex Findings emphasize that heterogeneity in hoarding symptomatology should be accounted for using homogenous subgroups reflecting presence or absence of other OCD symptoms, sex, and age group