Trichotillomania (hair-pulling) and excoriation (skin-picking) disorder are impairing body-focused repetitive behavior (BFRB) disorders that affect 1-3% of the population. While previous research demonstrates that these conditions run in families, the genetic architecture of BFRBs is still not well understood.
Our recent study, published in Translational Psychiatry, provides new insights into the genetics of BFRBs using genome-wide array data from parent-offspring trios affected by trichotillomania and/or excoriation disorder. By comparing the genetic profiles of affected offspring with those of their biological parents, we identified genetic factors that may contribute to the etiology of BFRBs, providing a strong foundation for larger-scale genomic studies of these understudied conditions.
Trichotillomania and excoriation disorder are currently classified as obsessive-compulsive related disorders (OCRDs) because of their clinical overlap and high co-occurrence with obsessive-compulsive disorder (OCD). Previous research suggests shared genetic factors between BFRBs and OCRDs, and prior work in OCD suggests the role of both common and rare genetic variants. We therefore set out to investigate genetic variants across the allele-frequency spectrum in a parent-offspring trio genomic study of trichotillomania and excoriation disorder, expecting to find evidence of shared genetic risk between BFRBs and OCD.
In this study, we collected and generated genome-wide array data from 110 families, each including at least one individual with trichotillomania and/or excoriation disorder and both of their biological parents. Building this cohort was a collaborative undertaking. We set up recruitment tables to collect DNA and information at the TLC Foundation for Body-Focused Repetitive Behaviors’ annual meetings. We also recruited in clinics and online through nonprofit organizations. Additional families were collected from a follow-up study of a pediatric trichotillomania clinical trial. These recruitment efforts allowed us to meet many families affected by these conditions. Talking with these families reinforced our commitment to better understand the causes of these understudied and often difficult-to-treat BFRBs.
When analyzing the data, we found that offspring with BFRBs showed a significant increased transmission of polygenic scores for OCD from their parents that was more than expected by chance. Polygenic scores are the summed effects of many common genetic variants that a person carries linked to a condition, with each variant nudging risk by a small amount. This finding is consistent with the clinical classification of trichotillomania and excoriation disorder as OCRDs and with the high co-occurrence of these conditions. Notably, we found that this enrichment of the OCD polygenic score transmission was of a similar magnitude and not statistically different between offspring with and without co-occurring OCD, suggesting that this observed over-transmission of the OCD polygenic score in individuals with BFRBs may not be fully attributed to a co-occurring OCD diagnosis. We also identified several rare copy number variants (stretches of DNA that are duplicated or missing) that were previously associated with neurodevelopmental conditions in individuals with BFRBs. Several of the genes affected by these copy number variants help neurons build and organize their connections, echoing other evidence pointing to synapse biology underlying these behaviors.
Overall, our results reinforce how genetic investigations of BFRBs may provide new insight into the biological underpinnings of these understudied conditions. Complex psychiatric disorders, such as BFRBs, may reflect an interplay of common and rare variation with different genetic factors contributing risk in different individuals, underscoring the need to consider the full spectrum of genetic variation. Larger cohorts with broad geographic representation are also essential to capture the genetic complexity of these disorders, along with the integration of environmental influences and other genetic factors that may likely shape the likelihood of developing a BFRB. Future studies that incorporate DNA sequencing, clinical assessment, and longitudinal follow-ups may help to further elucidate the biological underpinnings of BFRBs.
This research would not have been possible without the families affected by trichotillomania and excoriation disorder who generously shared their time and experiences to advance scientific progress in this field. We are also grateful for funding from the National Institutes of Health and foundations that supported this work. Moving forward, we hope to engage with more families and expand recruitment to include broad geographic representation. This is an especially important task in psychiatric genetics, where previous work has historically focused on European ancestry populations.
We also encourage the scientific community to build on this work. The genetic data from families who consented to data sharing are available to researchers through controlled access via the Database of Genotypes and Phenotypes (dbGaP), and we welcome other researchers to use them to push the field forward. Overall, our study advances the understanding of the genetic architecture of BFRBs. With continued collaboration between families and researchers, we are optimistic that genetic research will improve the lives of individuals and families affected by BFRBs.