The top two SNPs associated in the case-control meta-analysis (both with p<3×10-5 in the trio-case-control meta-analysis) are located in DLGAP1, another gene which influences glutamate signaling. DLGAP1 encodes a Shank-associated protein and has been associated with schizophrenia and with a smoking cessation phenotype69 and DLGAP1 deletions have also been observed (2 in schizophrenia cases versus 1 in controls).70 Another member of this gene family, DLGAP3, has been implicated in compulsive-like behavior in a mouse model (SAPAP3). Specifically, knockout mice for the striatum-expressed SAPAP3 gene (which codes for a post-synaptic protein at cortico-striatal glutamatergic excitatory synapses) developed repetitive grooming behaviors and anxiety that were reversed with an SSRI and with gene replacement.24
