Pilot study on HTR2A promoter polymorphism, −1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive–compulsive disorder

A previous study showed that a single nucleotide polymorphism (SNP), −1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive–compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous + 81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p = 0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5 years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to “normal” CNV and duplications); which is related to increased severity of OCD symptoms (p = 0.031; p = 0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p = 0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OCD.