On the other hand, there are several recent and ongoing studies of CHD8, a gene that has emerged as having the strongest association with autism spectrum disorder via the identification of multiple de novo LGD variants in unrelated parent-child trios (Figure S5) (39, 54–56). CHD8 is highly expressed in the developing brain (57). It encodes an ATP-dependent chromatin remodeler that binds to tri-methylated histone H3 lysine 4, a post-translational histone modification present at active promoters (58–60). Loss of CHD8 function appears to contribute to autism pathology by disrupting the expression of its target genes, which are themselves enriched for high confidence autism risk genes (57). While OCD subjects with de novo damaging CHD8 variants in our study do not meet any diagnostic criteria for autism, this finding suggests there may be overlapping biological mechanisms between the two disorders and leads us to hypothesize that genes regulated by CHD8 may similarly be enriched for OCD risk genes. Indeed, we see significant overlap between our OCD genes and ASD genes, as well as CHD8 gene targets mapped in the developing human brain (57) (Table 3, Table S6).
