08 Feb Study Finds Multiple Shared Genes Between Gastrointestinal and Psychiatric Disorders

MedicalResearch.com Interview with:

Dr. Zhongshang Yuan

Yuan, Zhongshang PhD
Department of Biostatistics
School of Public Health
Shandong University
Jinan, Shandong, China

What is the background for this study?

Response: 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, it is unclear the degree to which the shared genetic determinants contribute to these associations underlying GBA.

What are the main findings?

Response: This study focused on 4 gastrointestinal tract disease (inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, and gastro-oesophageal reflux disease) and 6 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, attention deficit hyperactivity disorder, posttraumatic stress disorder, and anorexia nervosa), resulting in 24 trait pairs, to explore the underlying shared genetic determinants. We found extensive genetic correlations and genetic overlaps among 22 out of 24 trait pairs. A total of 2,910 significant potential pleiotropic SNPs were identified in 19 trait pairs, with 83 pleiotropic loci and 24 colocalized loci detected. A total of 158 unique candidate pleiotropic genes were identified, which were highly enriched in certain GBA-related phenotypes and tissues, pathway enrichment analysis further highlighted biological pathways primarily involving cell adhesion, synaptic structure and function, and immune cell differentiation. Several identified pleiotropic loci also shared causal variants with gut microbiomes. Mendelian randomization analysis further illustrated vertical pleiotropy across 8 pairwise traits. Notably, many pleiotropic loci were identified for multiple pairwise traits, such as 1q32.1 (INAVA), 19q13.33 (FUT2), 11q23.2 (NCAM1), and 1p32.3 (LRP8).

What should readers take away from your report?

Response: The cutting-edge genome-wide pleiotropic analysis pipeline under the conceptual framework of GBA is highlighted. The pleiotropic variants and loci, genes as well as pathways shared between gastrointestinal tract diseases and psychiatric disorders were reported.

What recommendations do you have for future research as a result of this study?

Response: The results are mainly obtained from the genome-wide pleiotropic association analysis, , further experimental study is warranted to validate these findings.

Is there anything else you would like to add? Any disclosures?

Response: I have no conflicts of interest or other disclosures to report.

Citation:

Gong W, Guo P, Li Y, et al. Role of the Gut-Brain Axis in the Shared Genetic Etiology Between Gastrointestinal Tract Diseases and Psychiatric Disorders: A Genome-Wide Pleiotropic Analysis. JAMA Psychiatry. Published online February 08, 2023. doi:10.1001/jamapsychiatry.2022.4974

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Last Updated on February 8, 2023 by Marie Benz MD FAAD