Abstract

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) exhibit a high co-morbidity rate, similar symptoms, and a shared genetic basis. However, an understanding of the specific underlying mechanisms of these commonalities is currently limited. Here, we collected Genome-Wide Association Analysis results for AN and OCD, and obtained genes hit by the top SNPs as the risk genes. We then carried out an integrative coexpression network analysis to explore the convergence and divergence of AN and OCD risk genes. At first, we observed that the AN risk genes were enriched in coexpression modules that involved extracellular matrix functions and highly are expressed in the postnatal brain, limbic system, and non-neuronal cell types, while the OCD risk genes were enriched in modules of synapse function, the prenatal brain, cortex layers, and neurons. Next, by comparing the expressions from the eating disorder and OCD postmortem patient brain tissues, we observed both disorders have similar prefrontal cortex expression alterations influencing the synapse transmission, suggesting that the two diseases could have similar functional pathways. We found that the AN and OCD risk genes had distinct functional and spatiotemporal enrichment patterns but carried similar expression alterations as a disease mechanism, which may be one of the key reasons they had similar but not identical clinical phenotypes.

Highlights

  • Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are two distinct neuropsychiatric disorders but share a genetic basis [1,2,3]

  • To investigate the genetic association between AN and OCD, we first collected the implicated risk genes of AN and OCD identified from Genome-Wide Association Study (GWAS) summary statistics [25,26] (Table S1)

  • Previous studies did not observe the differences in brain regions or cell types involved in AN and OCD, we showed that the risk genes of the two diseases have such a distinction

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Summary

Introduction

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are two distinct neuropsychiatric disorders but share a genetic basis [1,2,3]. The prevalence of OCD is higher in AN patients than in the population [5]. The prevalence of AN is higher in OCD patients [6], which indicates significant co-morbidity between the two diseases. Clinicians have illustrated the characteristic phenotypes shared by AN and OCD: temporary relief for anxiety after obsessive–compulsive behaviors, followed by increasing long-term anxiety and fear [10]. These significant overlaps between AN and OCD has led some researchers to view them as part of an integrated spectrum, obsessive–compulsive spectrum disorders [11], indicating that they may be the different phenotypes of an identical pathology

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