The GRID2 gene is part of the glutamatergic signaling system (Pittenger, Bloch, and Williams 2011) which is thought to be important in OCD and is expressed in the brain regions which have been implicated in OCD (cerebellum, caudate, putamen, nucleus accumbens, and the anterior cingulate cortex) (Graybiel and Rauch 2000). Less is known about GPR135, however, results from the GTEx portal (https://gtexportal.org) indicate that it is also expressed in brain. Taken together, these results indicate that significant sex-specific effects for OCD likely exist but will be challenging to detect given their modest effect sizes and the sample size required to detect statistically robust genotype-sex interactions. Encouragingly, significant sex-stratified associations have been identified in studies of ASD and ADHD, demonstrating the value of increasing sample size for the study of sexually-differentiated genetic effects (Mitra et al. 2016; Martin, Walters, Demontis, Mattheisen, Lee, et al. 2017).
