Shared genetic susceptibilities for irritable bowel syndrome and depressive disorder in Chinese patients uncovered by pooled whole-exome sequencing

Abstract Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder presenting a high comorbidity with depressive disorder (DD). Many studies have confirmed that these two disease share the similar pathophysiology, but evidence of the genetic features is limited. This study aimed to analyze the genetic susceptibilities for IBS and DD in Chinese patients. Pooled whole-exome sequencing (pooled-WES) was performed to identify the candidate variants in 35 samples from each group of diarrhea predominant IBS (IBS-D) patients, DD patients, and healthy controls (HC). Then, targeted sequencing was used to validate the candidate variants in three additional cohorts of IBS-D, DD, and HC. Four variants associated with both IBS-D and DD through pooled-WES were identified, and three of them were validated in targeted sequencing. SYT8 rs3741231 G allele and SSPO rs12536873 TT genotype were associated with both IBS-D and DD. The genes of those variants are important in neurogenesis and neurotransmission. In addition, we found a unique risk variation COL6A1 rs13051496 for IBS-D. It increased the IBS-D risk and had a positive correlation with the scores of abdominal bloating and dissatisfaction of bowel habits. Through the results of this study, it provides a genetic basis for the high comorbidity of IBS-D and DD.