Dissection of the Genetic Association between Anorexia Nervosa and Obsessive–Compulsive Disorder at the Network and Cellular Levels

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.

Keywords

• anorexia nervosa
• co-morbidity
• network analysis
• obsessive-compulsory disorder
• risk genes