Psychiatric Disorders and Dietary Habits: An Investigation using Mendelian Randomization Analysis and Insights into Gene Expression Regulatory Mechanisms

Abstract

Abstract Background Dietary habits play a crucial role in life and may influence the development of psychiatric disorders (PD). Although observational studies have suggested an association between dietary habits and PD, establishing causality remains challenging due to confounding factors and study limitations. Methods In this study, we utilized dietary data from a vast cohort of over 500,000 participants recruited by the UK Biobank, along with genome-wide association study (GWAS) data for 11 PD. Leveraging two-sample Mendelian randomization (TSMR) and summary data-based Mendelian randomization (SMR) analyses, we integrated expression, methylation, and protein quantitative trait loci (eQTL, mQTL, and pQTL) data from brain tissue and blood. Results Our TSMR analyses revealed significant correlations between the intake of Cheese, Alcohol, and Dried fruit and multiple PD. SMR analyses identified several genes associated with these dietary habits, some of which were also linked to an increased risk of various PD. Furthermore, we observed a consistent association between the dietary habit-associated protein C1-Esterase Inhibitor and the risk of Insomnia, Major Depressive Disorder (MDD), and Neuroticism. Conclusions Our findings suggest a potential link between dietary habits and PD and shed light on plausible mechanisms underlying gene expression regulation. These results hold essential implications for future research on the pathogenesis of PD and the intricate relationship between diet and mental health. However, further investigations are warranted to validate and gain a deeper understanding of these associations, exploring additional contributing factors and elucidating the underlying mechanisms.