Role of the Gut-Brain Axis in the Shared Genetic Etiology Between Gastrointestinal Tract Diseases and Psychiatric Disorders

Comorbidities and genetic correlations between gastrointestinal tract diseases and psychiatric disorders have been widely reported, with the gut-brain axis (GBA) hypothesized as a potential biological basis. However, the degree to which the shared genetic determinants are involved in these associations underlying the GBA is unclear.

To investigate the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders and to identify shared genomic loci, genes, and pathways. Design, Setting, and Participants: This genome-wide pleiotropic association study using genome-wide association summary statistics from publicly available data sources was performed with various statistical genetic approaches to sequentially investigate the pleiotropic associations from genome-wide single-nucleotide variation (SNV; formerly single-nucleotide polymorphism [SNP]), and gene levels and biological pathways to disentangle the underlying shared genetic etiology between 4 gastrointestinal tract diseases (inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, and gastroesophageal reflux disease) and 6 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and anorexia nervosa). Data were collected from March 10, 2021, to August 25, 2021, and analysis was performed from January 8 through May 30, 2022. Main Outcomes and Measures: The primary outcomes consisted of a list of genetic loci, genes, and pathways shared between gastrointestinal tract diseases and psychiatric disorders.