The following is a summary of “Role of the Gut-Brain Axis in the Shared Genetic Etiology Between Gastrointestinal Tract Diseases and Psychiatric Disorders,” published in the February 2023 issue of Psychiatry by Gong, et al.
Numerous studies have documented the hereditary and comorbid relationships between psychiatric disorders and gastrointestinal disorders, with the gut-brain axis (GBA) being proposed as a possible molecular underpinning. For a study, researchers sought to investigate the potential shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders and to identify the specific genetic loci, genes, and pathways involved.
The research utilized publicly available genome-wide association summary statistics and various statistical genetic approaches to sequentially analyze the pleiotropic associations at different levels, ranging from single-nucleotide variations (SNVs) to genes and biological pathways. The analysis focused on four types of gastrointestinal tract diseases (inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, and gastroesophageal reflux disease) and six psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and anorexia nervosa). The data were collected from March 10, 2021, to August 25, 2021, and the analysis was conducted from January 8 to May 30, 2022. The study’s primary outcomes included a list of shared genetic loci, genes, and pathways contributing to the associations between gastrointestinal tract diseases and psychiatric disorders.
Among 24 pairs of traits, extensive genetic overlaps and correlations were discovered in 22 pairs. A pleiotropic analysis conducted under a composite null hypothesis revealed 2,910 potential pleiotropic single-nucleotide variations (SNVs) in 19 trait pairs, of which 83 pleiotropic loci and 24 colocalized loci were detected. A gene-based analysis found 158 unique candidate pleiotropic genes significantly enriched in specific GBA-related phenotypes and tissues. Pathway enrichment analysis highlighted biological pathways primarily involving cell adhesion, synaptic structure, and function, and immune cell differentiation. In addition, some pleiotropic loci were found to share causal variants with gut microbiomes. Vertical pleiotropy across 8 pairwise traits was demonstrated through Mendelian randomization analysis. Notably, many pleiotropic loci, such as 1q32.1 (INAVA), 19q13.33 (FUT2), 11q23.2 (NCAM1), and 1p32.3 (LRP8), were identified for multiple pairwise traits.
The findings implied the genome-wide distribution of the pleiotropic genetic factors between psychiatric disorders and diseases of the gastrointestinal system. The findings have significant implications for both the disease targets for management and treatment while supporting the GBA’s shared genetic origin.
Source: jamanetwork.com/journals/jamapsychiatry/fullarticle/2801422
