Obsessive compulsive disorder (OCD) is a syndrome characterized by recurrent and 
intrusive thoughts and ritualistic behaviors or mental acts that a person feels 
compelled to perform. Twin studies, family studies, and segregation analyses 
provide compelling evidence that OCD has a strong genetic component. The SLITRK1 
gene encodes a developmentally regulated stimulator of neurite outgrowth and 
previous studies have implicated rare variants in this gene in disorders in the 
OC spectrum, specifically Tourette syndrome (TS) and trichotillomania (TTM). The 
objective of the current study was to evaluate rare genetic variation in SLITRK1 
in risk for OCD and to functionally characterize associated coding variants. We 
sequenced SLITRK1 coding exons in 381 individuals with OCD as well as in 356 
control samples and identified three novel variants in seven individuals. We 
found that the combined mutation load in OCD relative to controls was 
significant (p = 0.036). We identified a missense N400I change in an individual 
with OCD, which was not found in more than 1000 control samples (P<0.05). In 
addition, we showed the the N400I variant failed to enhance neurite outgrowth in 
primary neuronal cultures, in contrast to wildtype SLITRK1, which enhanced 
neurite outgrowth in this assay. These important functional differences in the 
N400I variant, as compared to the wildtype SLITRK1 sequence, may contribute to 
OCD and OC spectrum symptoms. A synonymous L63L change identified in an 
individual with OCD and an additional missense change, T418S, was found in four 
individuals with OCD and in one individual without an OCD spectrum disorder. 
Examination of additional samples will help assess the role of rare SLITRK1 
variation in OCD and in related psychiatric illness.