Department of Biochemistry and Medical Genetics, University of Manitoba, Room 308-Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, ON, M5T 3M7, Canada.
J Transl Med. 2022 Jan 27;20(1):43. doi: 10.1186/s12967-022-03242-9.
Approximately 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.
The 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.
The estimated PRS had a significantly positive association with PC status (for the highest effect: P-value threshold = 5 × 10, odds ratio = 2.0, P-value = 1.5 × 10). 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.
PC 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.
约 40%的炎症性肠病（IBD）患者存在精神共病（PC）。先前的研究表明，IBD 和 PC 都具有多基因遗传效应。在这项研究中，我们评估了遗传变异在 IBD 人群 PC 中的作用。此外，我们还评估了这种影响是否由我们之前的研究中确定的 RBPMS 基因的表达水平介导，该基因被认为是 IBD 患者 PC 的潜在危险因素。
使用来自马尼托巴 IBD 队列研究的欧洲血统的 IBD 患者（n=240）的外部全基因组关联研究（GWAS）来估计多基因风险评分（PRS）。检验了在 IBD 患者中，估计的 PRS 与 PC 状态之间的关联和预测性能。最后，应用基于回归的模型来探索 RBPMS 基因的推断表达水平是否是 PRS 和 IBD 中 PC 状态之间的中介因素。
估计的 PRS 与 PC 状态呈显著正相关（最高效应：P 值阈值=5×10，优势比=2.0，P 值=1.5×10）。PRS 和 IBD 中 PC 状态之间的因果效应约有 13%是由 RBPMS 基因的表达水平介导的。基于 PRS 的 PC 预测模型的曲线下面积在 5×10 的阈值下约为 0.7。
IBD 中的 PC 状态取决于欧洲血统人群中的遗传影响。PRS 可用于 PC 风险筛查，以识别 PC 风险较高的 IBD 患者。这种遗传影响约有 13%可以由 RBPMS 基因的表达水平来解释。
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