Abstract
ObjectivesDeciphering the genetic relationships between major depressive disorder (MDD) and atopic diseases (asthma, hay fever, and eczema) may facilitate understanding of their biological mechanisms as well as the development of novel treatment regimens. Here we tested the genetic correlation between MDD and atopic diseases by linkage disequilibrium score regression.MethodsA polygenic overlap analysis was performed to estimate shared genetic variations between the two diseases. Causal relationships between MDD and atopic diseases were investigated using two-sample bidirectional Mendelian randomization analysis. Genomic loci shared between MDD and atopic diseases were identified using cross-trait meta-analysis. Putative functional genes were evaluated by fine-mapping of transcriptome-wide associations.ResultsThe polygenic analysis revealed approximately 15.8 thousand variants causally influencing MDD and 0.9 thousand variants influencing atopic diseases. Among these variants, approximately 0.8 thousand were shared between the two diseases. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on atopic diseases (b = 0.22, p = 1.76 × 10-6), while genetic liability to atopic diseases confers a weak causal effect on MDD (b = 0.05, p = 7.57 × 10-3). Cross-trait meta-analyses of MDD and atopic diseases identified 18 shared genomic loci. Both fine-mapping of transcriptome-wide associations and analysis of existing literature suggest the estrogen receptor β-encoding gene ESR2 as one of the potential risk factors for both MDD and atopic diseases.ConclusionOur findings reveal shared genetic liability and causal links between MDD and atopic diseases, which shed light on the phenotypic relationship between MDD and atopic diseases.
Highlights
Mental disorders confer a heavy burden on society [1]
Mendelian randomization analysis indicates that genetic liability to Major depressive disorder (MDD) has a causal effect on atopic diseases (b = 0.22, p = 1.76 × 10-6), while genetic liability to atopic diseases confers a weak causal effect on MDD (b = 0.05, p = 7.57 × 10-3)
We explore whether the genes shared by MDD and atopic diseases (ADs) have been identified in previous genome-wide association studies
Summary
Mental disorders confer a heavy burden on society [1]. Major depressive disorder (MDD), the most prevalent mental disorder accompanied by considerable morbidity, mortality, and risk of suicide, is characterized by persistent low mood [2]. When comorbid with other ailments, for example, atopic diseases (ADs), MDD produces worse clinical outcomes and incurs higher healthcare costs. Three kinds of common ADs, namely, asthma, hay fever (allergic rhinitis), and eczema (atopic dermatitis), may coexist in the same individuals [4]. A chronic airway disease that is common worldwide, is characterized by coughing, wheezing, shortness of breath, and/or chest tightness due to increased airway reactivity, inflammation, and/or mucus production. Eczema is an inflammatory skin disease that is caused by a dysfunction of a skin barrier followed by aberrant inflammation/immune responses; this disease is affecting 5% of the population worldwide [7]. Allergic rhinitis has been shown to have a positive association with MDD (odds ratio: 1.24) [8]. Atopic eczema is associated with an increased incidence of new depression (hazard ratio: 1.14) [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
