Association of intestinal anti-inflammatory drug target genes with psychiatric Disorders: A Mendelian randomization study

作者：Guorui Zhao, Zhe Lu, Yundan Liao, Yaoyao Sun, Yuyanan Zhang, Zhewei Kang, Xiaoyang Feng, Junyuan Sun, Weihua Yue · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.05.002 · 被引用次数：16 · 研究领域：Gut microbiota and health、Genetic Associations and Epidemiology、Tryptophan and brain disorders

Psychiatric disorders present a substantial global public health burden with limited drug options. The gut-brain axis connects inflammatory bowel diseases and psychiatric disorders, which often have comorbidities. While some evidence hints at anti-inflammatory drugs aiding in treating psychiatric conditions, the specific effects of intestinal anti-inflammatory drugs remain unclear. This study investigates the causal effect of intestinal anti-inflammatory drug targets on psychiatric disorders. We hypothesize that these drug targets may offer new insights into the treatment and prevention of such disorders. Additionally, we explore gut microbiota’s mediating role between drug target genes and psychiatric disorders. We performed two-sample Mendelian randomization (MR) using summary data from existing expression quantitative trait loci (eQTL) and protein QTL in the brain, along with public genome-wide association studies of disease. We also explored gut microbiota’s mediating effect. The statistics encompassed six psychiatric disorders involving 9,725–500,199 individuals. Colocalization analysis enhanced the MR evidence. We uncovered a causal link between TPMT (a target of olsalazine) expression in the amygdala and bipolar disorder (BD) risk (odds ratio [OR] = 1.08; P = 4.29 × 10−4). This association was observed even when the sigmoid colon and whole blood eQTL were considered as exposures. Colocalization analysis revealed a shared genetic variant (rs11751561) between TPMT expres...