School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Genes (Basel). 2021 Mar 27;12(4):491. doi: 10.3390/genes12040491.
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.
神经性厌食症 (AN) 和强迫症 (OCD) 具有较高的共病率、相似的症状和共同的遗传基础。然而，目前对于这些共同特征的具体潜在机制的理解还很有限。在这里，我们收集了 AN 和 OCD 的全基因组关联分析结果，并获得了被 top SNPs 命中的基因作为风险基因。然后，我们进行了综合共表达网络分析，以探索 AN 和 OCD 风险基因的趋同和分歧。首先，我们观察到 AN 风险基因在涉及细胞外基质功能的共表达模块中富集，并在出生后大脑、边缘系统和非神经元细胞类型中高度表达，而 OCD 风险基因在突触功能模块、产前大脑、皮质层和神经元中富集。接下来，通过比较进食障碍和 OCD 尸检患者脑组织中的表达情况，我们观察到两种疾病都有类似的前额叶皮层表达改变，影响突触传递，这表明这两种疾病可能有相似的功能途径。我们发现，AN 和 OCD 风险基因具有不同的功能和时空富集模式，但作为疾病机制具有相似的表达改变，这可能是它们具有相似但不完全相同的临床表型的关键原因之一。
