Following on from previous work by our group where we showed that early onset anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) shared a common genetic background, the aim of the present study is to assess genetic pleiotropy related to the serotonergic system (SLC6A4, 5HTR2A, 5HTR2C, TPH2, SLC18A1), in a common phenotype such as very-early age of onset.
Five SNPs achieved 0.004 (the nominal p-value expected by chance), 3 with empirical significant p-values (rs10070190 (CDH9) p = 1 × 10(-3), rs4825476 (GRIA3) p = 4 × 10(-4), and rs1074815 (TPH2) p = 8 × 10(-4)) and 2 additional polymorphisms showing nominal significance (rs2834070 (OLIG2) p = 2 × 10(-3) and rs11783752 (SCL18A1) p = 3 × 10(-3)), were found to be related to both AN and OCD.
As several other uncommon, less well quantitated genetic variations occur with an OCD phenotype, including chromosomal anomalies and some other rare gene variants (SGCE, GCH1 and SLITRK1), a tentative conclusion is that OCD resembles other complex disorders in being etiologically heterogeneous and in having both highly penetrant familial subtypes associated with rare alleles or chromosomal anomalies, as well as having a more common, polygenetic form that may involve polymorphisms in such genes as BDNF, COMT, GRIN2beta, TPH2, HTR2A and SLC1A1.
Stereotypic and repetitive behaviors are influenced by 5-HT, and initial studies report an association of TPH2 alleles with childhood-onset obsessive-compulsive disorder (OCD) and with autism.
In conclusion, the results link TPH2 variations to the pathogenesis of early-onset OCD and further support the aetiological relevance of 5-HT signalling in OCD.