Mendelian randomization study on the causal effects of systemic lupus erythematosus on major depressive disorder

Abstract

The vast majority of epidemiological studies suggested a link between systemic lupus erythematosus (SLE) and major depressive disorder (MDD). However, the causality for SLE on the risk of MDD remained unknown due to confounding factors or reverse causality. Herein, we investigated the causality between SLE and MDD in those of European ancestry by a Mendelian randomization (MR) approach. Summary genetic data of cases with SLE/MDD were derived from independent largest public genome-wide association study. Forty-six single nucleotide polymorphisms associated with SLE were used as instrumental variables. The main causal inference was carried out using the MRE-IVW method. Additional, reverse-direction MR and multivariable MR analyses were further performed. Result indicated that SLE was causally associated with a lower risk of MDD (using the MRE-IVW method, odds ratio [OR] = 0.983, 95% confidence interval [CI] = 0.974–0.991, p = 1.18 × 10−4). Complementary analysis found no heterogeneity or horizontal pleiotropy. Multivariate MR analysis yielded consistent results (OR = 0.981; 95% CI = 0.969–0.993; p = 2.75 × 10−3). Reverse-direction MR analysis suggested non-causal relationship of MDD on the risk of SLE (using the IVW method, OR = 0.846, 95% CI = 0.345–2.072; p = 0.714). Thus, this is the first study providing evidence of potential causal links between SLE and MDD and further related research is needed.

Dissecting the association between gut microbiota and hypertrophic scarring: a bidirectional Mendelian randomization study

“…Furthermore, a reverse model was implemented to estimate the effect of hypertrophic scarring on gut microbiota. This analysis aimed to explore the potential existence of a reverse-direction causal relationship, assessing whether the exposure is positioned upstream of the outcome ( Li W et al, 2023 ). Reverse MR is a relatively less common approach compared to standard MR analyses, but it can provide insights into the potential causal relationships between outcomes and exposures, especially in situations where conventional study designs may face challenges.…”

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

“…MDD modulates the initiation and/or episodic symptom exacerbations of most 'autoimmune'/'immune-mediated' disorders, including multiple sclerosis [184], rheumatoid arthritis [183], Alzheimer's disease [185], Parkinson's disease [186] and SLE [187], indicating the role that MDD pathophysiology has in their course. MDD pathophysiology includes gut dysbiosis/permeability, pro-inflammatory cytokines, IDO induction and the conversion of tryptophan to kynurenine, leading to enhanced AhR activation, thereby dysregulating the tryptophan-melatonin pathway [188], and allowing the MDD pathophysiology to be intimately linked to the pathophysiological processes underpinning 'autoimmune' disorders.…”

Genetic Comorbidity of Depression and Somatic Diseases: Rationale Study Design in a Population Cohort Using Polygenic Risk Scores

“…В последнее время получено большое количество данных о существовании значительного уровня генетического перекреста депрессии и различных хронических соматических заболеваний на основе GWAS и PRS, а также с применением метода менделевской рандомизации (Mendelian randomization). Среди таких заболеваний важно отметить ожирение [23,24], в том числе детское ожирение [25]; аутоиммунные заболевания, в том числе ревматоидный артрит [26] и системную красную волчанку [27]; гипертензию [28] и сердечно-сосудистые заболевания [29], в частности инфаркт миокарда и ишемическую болезнь сердца [30]. Важное место отводится воспалению в целом [31].…”