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Abstract
BackgroundApproximately 40% of persons with inflammatory bowel disease (IBD) experience psychiatric comorbidities (PC). Previous studies demonstrated the polygenetic effect on both IBD and PC. In this study, we evaluated the contribution of genetic variants to PC among the IBD population. Additionally, we evaluated whether this effect is mediated by the expression level of the RBPMS gene, which was identified in our previous studies as a potential risk factor of PC in persons with IBD.Materials and methodsThe polygenic risk score (PRS) was estimated among persons with IBD of European ancestry (n = 240) from the Manitoba IBD Cohort Study by using external genome-wide association studies (GWAS). The association and prediction performance were examined between the estimated PRS and PC status among persons with IBD. Finally, regression-based models were applied to explore whether the imputed expression level of the RBPMS gene is a mediator between estimated PRS and PC status in IBD.ResultsThe estimated PRS had a significantly positive association with PC status (for the highest effect: P-value threshold = 5 × 10–3, odds ratio = 2.0, P-value = 1.5 × 10–5). Around 13% of the causal effect between the PRS and PC status in IBD was mediated by the expression level of the RBPMS gene. The area under the curve of the PRS-based PC prediction model is around 0.7 at the threshold of 5 × 10–4.ConclusionPC status in IBD depends on genetic influences among persons with European ancestry. The PRS could potentially be applied to PC risk screening to identify persons with IBD at a high risk of PC. Around 13% of this genetic influence could be explained by the expression level of the RBPMS gene.
Highlights
Inflammatory bowel disease (IBD) is a chronic immunologically mediated disease affecting the gastrointestinal tract which is manifested by diarrhea, rectal bleeding, and abdominal pain
Causal mediation analysis In order to understand how different polygenic risk score (PRS) will result in different psychiatric comorbidities (PC) status in persons with inflammatory bowel disease (IBD) of European ancestry, we further examined whether the association between PRS and PC status was mediated by the expression level of the RBPMS gene
Our results showed that the PRS was significantly associated with the PC status in IBD at P-value thresholds of 5 × 10–3 and 5 × 10–4 when PRS was estimated based on the IBD genome-wide association studies (GWAS)
Summary
Inflammatory bowel disease (IBD) is a chronic immunologically mediated disease affecting the gastrointestinal tract which is manifested by diarrhea, rectal bleeding, and abdominal pain. 40% of persons with IBD experience psychiatric comorbidity (PC), such as depression and anxiety [4], which is significantly higher than in the general population [5]. Comorbid psychiatric illness could lead to a higher risk of disease relapse and poorer response to treatment [6,7,8]. Identifying IBD patients with a higher risk of PC could improve the longterm treatment outcome. 40% of persons with inflammatory bowel disease (IBD) experience psychiatric comorbidities (PC). Previous studies demonstrated the polygenetic effect on both IBD and PC. We evaluated whether this effect is mediated by the expression level of the RBPMS gene, which was identified in our previous studies as a potential risk factor of PC in persons with IBD
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