There is a bidirectional causal connection between GERD and major depressive disorder.

This study was carried out to determine the causal link between major depressive disorder (MDD) and gastroesophageal reflux disease (GERD).

From pertinent genome-wide association studies, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium were chosen for the instrumental variables of MDD and GERD, respectively, at the genome-wide significance level.

In this bidirectional Mendelian randomization study, the summary-level genetic data were sorted from genome-wide association studies encompassing 173,005 people (113,154 non-cases; 59,851 cases), 385,276 people (305,011 non-cases; 80,265 cases), 463,010 people (458,650 non-cases; 4360 cases), and 383,916 people (371,349 non-cases; 12,567 cases) for MDD, GERD, GERD without esophagitis, and reflux esophagitis.

GERD and its subtypes were positively related to genetic susceptibility to severe depressive disorder. For the per one-unit rise in the log-transformed odds ratio of MDD, the odds ratios for GERD, GERD without esophagitis, and reflux esophagitis were 1.31, 1.51, and 1.21, respectively.

Reverse-direction study revealed that genetic vulnerability to GERD was directly connected to the rising risk of major depressive illness. The odds ratio of MDD was 1.28 for every unit rise in the log-transformed odds ratio of GERD.

Significant attention should be paid to MDD prevention in GERD people along with GERD prevention in people with an elevated risk of depression.