A genomic study of trichotillomania and excoriation disorder in families

Trichotillomania and excoriation disorder are obsessive-compulsive related disorders that are often subclassified together as body-focused repetitive behavior (BFRB) disorders. While previous research suggests shared genetic factors, the genetic architecture of these BFRBs remains incompletely understood. Probands with trichotillomania and/or excoriation disorder and both of their biological parents were recruited for an ongoing genetic study of parent-offspring trios with BFRBs. Genome-wide array data were generated in 110 families (334 individuals total) to investigate the role of both common single-nucleotide polymorphisms and rare copy-number variants (CNVs). Polygenic scores were calculated using summary statistics from genome-wide association studies of related psychiatric conditions, including obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder. Using the polygenic transmission disequilibrium test (pTDT), we observed a significant over-transmission of the OCD polygenic score in probands of European ancestry from their parents (mean pTDT = 0.36, p = 0.01, n = 92), and a non-significant enrichment for the other conditions. Our results suggest that common variants associated with OCD may contribute to risk for BFRBs, consistent with their current classification as obsessive-compulsive related disorders. We also identified several rare CNVs in probands that overlapped genes intolerant to loss-of-function (LoF) mutations and those previously associated with neurodevelopmental disorders. The LoF-intolerant genes were enriched in biological processes relevant to synapse organization and neurodevelopment. This work provides new insight into the genetic underpinnings of these BFRB disorders, paving the way for larger genomic studies of these understudied conditions.