Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry

Abstract

Background Major depressive disorder (MDD) is clinically documented to co-occur with multiple gastrointestinal disorders (GID), but the potential causal relationship between them remains unclear. We aimed to evaluate the potential causal relationship of MDD with 4 GID [gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), peptic ulcer disease (PUD), and non-alcoholic fatty liver disease (NAFLD)] using a two-sample Mendelian randomization (MR) design. Methods We obtained genome-wide association data for MDD from a meta-analysis (N = 480 359), and for GID from the UK Biobank (N ranges: 332 601–486 601) and FinnGen (N ranges: 187 028–218 792) among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of sensitivity analyses to test the hypothesis of MR. Individual study estimates were pooled using fixed-effect meta-analysis. Results Meta-analyses IVW MR found evidence that genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Additionally, reverse MR found evidence of genetically predicted GERD or IBS may increase the risk of MDD. Conclusions Genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Genetically predicted GERD or IBS may increase the risk of MDD. The findings may help elucidate the mechanisms underlying the co-morbidity of MDD and GID. Focusing on GID symptoms in patients with MDD and emotional problems in patients with GID is important for the clinical management.

Machine learning-based integration identifies the ferroptosis hub genes in nonalcoholic steatohepatitis

“…The 16 FRGs identified in this study are widely implicated in various metabolic pathways, such as “metabolism of alpha-linolenic acid,” “fat cell differentiation,” “regulation of fat cell differentiation,” and “circadian rhythm genes.” Notably, these genes have been linked to the causes of NASH, such as “fatty liver disease,” “dyslipidemias,” “insulin resistance,” “gestational diabetes,” and “unipolar depression” [ 37 – 41 ]. Sixteen FRGs were processed further.…”

Machine learning-based integration identifies ferroptosis hub genes in nonalcoholic steatohepatitis

“…Evidently, these 16 genes exhibited a predilection for pathways pertinent to metabolism, encompassing domains such as "metabolism of alpha-linolenic acid", "fat cell differentiation", "regulation of fat cell differentiation", and "Circadian rhythm genes". Intriguingly, these genes demonstrated conspicuous links to the underpinnings and determinants of NASH, encapsulated by associations with conditions such as "fatty liver disease", "dyslipidemias", "insulin resistance", "gestational diabetes", and "unipolar depression" [36][37][38][39][40]. Furthermore, an endeavor was undertaken to discern the quintessential ferroptosis-related hub genes in NASH, employing 113 machine-learning algorithms.…”

A comprehensive Mendelian randomization study highlights the relationship between psychiatric disorders and non-tumor gastrointestinal diseases

“…However, most of these studies have primarily focused on a single type of gastrointestinal disease, such as IBD ( Yang et al, 2023 ) or IBS ( Zhang et al, 2024 ). There are also some contradictory results, for instance, Youjie Zeng and others demonstrated that anxiety and depression do not increase the risk of gastroesophageal reflux disease ( Zeng et al, 2023 ), while other experiments have arrived at the opposite conclusion ( Chen et al, 2023 ; Zou et al, 2023 ). Therefore, in order to more comprehensively explore the potential relationship between the two, we have selected a broader range of psychiatric diseases and gastrointestinal diseases, as well as multiple datasets that differ from those used in previous studies, to provide more robust evidence.…”