Furthermore, we observed that SDEs, SNPs with the greatest heterogeneity in effect size between males and females were enriched for gene regulatory function (eQTLs) in brain and immune tissues, implicating these tissues in sexual-differentiation of OCD. The enrichment of immune eQTLs among SDEs is consistent with both the known role of the immune system in several neuropsychiatric traits (Schizophrenia Working Group of the Psychiatric Genomics Consortium 2014; Furtado and Katzman 2015a, [b] 2015; Murphy, Sajid, and Goodman 2006), and the observed sex differences in immune function (Klein and Flanagan 2016). Moreover, a recent whole-exome sequencing study found that OCD probands have a higher rate of de novo nonsynonymous single-nucleotide variants in genes enriched for neurodevelopmental and immunological processes (Cappi et al. 2016). Though specific mechanisms remain unknown, these studies provide new evidence for an old hypothesis linking the immune system with compulsive behavior and OCD (Marazziti et al. 1999; Kawikova et al. 2007; Murphy, Sajid, and Goodman 2006; Slattery et al. 2004; Miguel et al. 1995; Swedo et al. 1998; Murphy et al. 2012; Snider and Swedo 2004; Swedo et al. 2012; Leonard et al. 1992; Carapetis and Currie 1999).
