Investigating Causality and Shared Genetic Architecture between Neurodegenerative Disorders and Inflammatory Bowel Disease

• DOI: 10.14336/ad.2022.12209
• Publication Date: 2023-03-22T09:31:26Z
• Authors: Ruijie Zeng; Jinghua Wang; Rui Jiang; Jie Yang; Chunwen Zheng; Huihuan Wu; Zewei Zhuo; Qi Yang; Jingwei Li; Felix W Leung; Weihong Sha; Hao Chen
• Keywords: Mendelian Randomization; Genetic architecture; Genetic predisposition; Genome-wide Association Study; Causality; Genetic Association; Multifactorial Inheritance

Published observational studies have revealed the connection between neurodegenerative disorders and inflammatory bowel disease (IBD), whereas causal association remains largely unclear. Our study aims to assess causality identify shared genetic architecture IBD. Two-sample Mendelian randomization analyses were performed IBD (amyotrophic lateral sclerosis [ALS], Alzheimer's [AD], Parkinson's [PD], multiple [MS]). Shared loci, functional interpretation, transcriptomic profiles further investigated in ALS We identified that predisposition was suggestively associated with lower odds of (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94 0.99). In contrast, not genetically an increased risk AD, PD, or MS (and vice versa). Two loci (rs6571361 rs7154847) derived, SCFD1, G2E3, HEATR5A as novel genes enriched functions related membrane trafficking. G2E3 differentially expressed significantly correlated SCFD1 patients reveals protective role on ALS, does support findings indicate possible pathways These results provide insights into pathogenesis therapeutics disorders.