Dissecting shared genetic susceptibility between gastroesophageal reflux disease and psychiatric disorders beyond body mass index
- 1College of Medical Information and Artificial Intelligence, Shandong First Medical University, Shandong, China.
Abstract
Gastroesophageal reflux disease (GERD) exhibits substantial comorbidity with psychiatric disorders, yet the biological basis underlying this relationship remains unclear. Here, we integrated large-scale GWAS meta-analysis, Mendelian randomization, Genomic Structural Equation Modeling, local genetic correlation analysis, and single-cell transcriptomic enrichment mapping to investigate the shared genetic architecture linking GERD, psychiatric disorders, and body mass index (BMI). GERD demonstrated strongest genetic overlap with internalizing psychiatric disorders, particularly major depressive disorder and post-traumatic stress disorder, whereas the relationship with BMI was comparatively weaker and lacked significant bidirectional causal effects. Genomic SEM further showed that GERD preferentially loaded onto an internalizing latent factor independent of obesity-related liability. At the cellular level, GERD-associated genetic signals localized predominantly to interoceptive and limbic brain systems involved in visceral sensation, stress responsivity, and autonomic regulation. Together, these findings support a distinct neuropsychiatric component underlying GERD susceptibility and implicate centrally mediated brain-gut mechanisms beyond metabolic dysfunction.
Related
- Perinatal insults, genetic susceptibility, and the pathogenesis of neurodevelopmental disorders: from epigenetic remodeling to neural circuit dysfunction—a narrative review
- Exome-wide rare variant genetic load is associated with cognition, intellectual disability and psychiatric disorders in population-based cohorts
- Leveraging Shared Genetic Architecture Between Psychiatric and Other Medical Disorders Increases Power and Reveals Novel Psychiatric Risk Loci
- Vitamin D–VDR Signaling Across Thyroid Disorders: A Systematic Review of Molecular Mechanisms, Autoimmunity, Genetic Susceptibility, Experimental Evidence and Therapeutic Translation
- Microglia in Psychiatric Disorders: Stage-Dependent Roles and Therapeutic Implications
BibTeX
@misc{wang2026dissecting,
title = {{Dissecting shared genetic susceptibility between gastroesophageal reflux disease and psychiatric disorders beyond body mass index}},
author = {X. Wang and Q. Zhang and Q. Wu and M. Zhang and Z. Liu and F. Hu and Y. Zhou and H. Yu and K. Ullah and N. Zhang and Y. Song and H. Zhao and X. Chang},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.26364056},
url = {https://www.medrxiv.org/content/10.64898/2026.09.26.26364056v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Dissecting shared genetic susceptibility between gastroesophageal reflux disease and psychiatric disorders beyond body mass index
AU - X. Wang
AU - Q. Zhang
AU - Q. Wu
AU - M. Zhang
AU - Z. Liu
AU - F. Hu
AU - Y. Zhou
AU - H. Yu
AU - K. Ullah
AU - N. Zhang
AU - Y. Song
AU - H. Zhao
AU - X. Chang
PY - 2026
DA - 2026/09/26
PB - medRxiv
DO - 10.64898/2026.09.26.26364056
UR - https://www.medrxiv.org/content/10.64898/2026.09.26.26364056v1
AB - Gastroesophageal reflux disease (GERD) exhibits substantial comorbidity with psychiatric disorders, yet the biological basis underlying this relationship remains unclear. Here, we integrated large-scale GWAS meta-analysis, Mendelian randomization, Genomic Structural Equation Modeling, local genetic correlation analysis, and single-cell transcriptomic enrichment mapping to investigate the shared genetic architecture linking GERD, psychiatric disorders, and body mass index (BMI). GERD demonstrated strongest genetic overlap with internalizing psychiatric disorders, particularly major depressive disorder and post-traumatic stress disorder, whereas the relationship with BMI was comparatively weaker and lacked significant bidirectional causal effects. Genomic SEM further showed that GERD preferentially loaded onto an internalizing latent factor independent of obesity-related liability. At the cellular level, GERD-associated genetic signals localized predominantly to interoceptive and limbic brain systems involved in visceral sensation, stress responsivity, and autonomic regulation. Together, these findings support a distinct neuropsychiatric component underlying GERD susceptibility and implicate centrally mediated brain-gut mechanisms beyond metabolic dysfunction.
ER -