Cerebral cortex changes in FD, IBS, and GERD: A Mendelian randomization study

Abstract

BackgroundProspective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship is unclear. Therefore, we used Mendelian randomization (MR) to determine the causal effects of common gastrointestinal disorders on cortical structures. MethodsGenome-wide association study (GWAS) data for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) were obtained from 329,262, 16,792, and 602,604 Europeans, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR–Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy. ResultsThe results revealed that FD significantly decreases the TH in the rostral anterior cingulate cortex (βTH = −0.022 mm; 95%CI: −0.035 mm to −0.009 mm2; PTH = 6.89 × 10−4), and IBS significantly decreases the SA of the pars triangularis (βSA = −21.91 mm2; 95%CI: −32.99 mm to −10.83 mm2; PSA = 1.06 × 10−4), precuneus (βSA = −47.53 mm2; 95%CI: −73.57 mm to-21.48 mm2; PSA = 3.48 × 10−4) and superior frontal regions (βSA = −78.70 mm2; 95%CI: −122.61 mm to −34.78 mm2; PSA = 4.4 × 10−4). At the local functional level, GERD significantly increases the SA of the inferior temporal region (βSA = −113.58 mm2, 95%CI: −113.58 mm to −39.01 mm2, PSA = 6.05 × 10−5). ConclusionsFD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, thus increasing the risks of mental illness and cognitive dysfunction.