Shared Genetic Liability Between Major Depressive Disorder and Atopic Diseases

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.

Genetic liability to asthma and risk of cardiovascular diseases: A Mendelian randomization study

“…First, although we have excluded potential pleiotropic SNPs and MR-Egger regression indicated little horizontal pleiotropy, the influence of pleiotropy bias remains a concern in this study. Specifically, psychiatric traits such as major depressive disorder and neuroticism may be confounding factors in the causal associations between asthma and CVDs ( Cao et al, 2021 ; Wu et al, 2021 ; Zhang et al, 2021 , 2022 ). Besides, the divergent results of sensitivity analyses may indicate a bias of genetic pleiotropy towards asthma-AF and asthma-HF associations that we observed.…”

Assessing Causal Associations of Atopic Dermatitis With Heart Failure and Other Cardiovascular Outcomes: A Mendelian Randomization Study

“…Future studies on other populations are therefore warranted. Second, some psychiatric traits (such as major depressive disorder (MDD) and neuroticism) shared genetic liability with AD and CVDs ( 53 – 55 ). Specifically, there is a bidirectional causal association between MDD and AD ( 53 ), and MDD can lead to a higher risk of CVDs ( 54 ).…”

“…Second, some psychiatric traits (such as major depressive disorder (MDD) and neuroticism) shared genetic liability with AD and CVDs ( 53 – 55 ). Specifically, there is a bidirectional causal association between MDD and AD ( 53 ), and MDD can lead to a higher risk of CVDs ( 54 ). Therefore, the influence of potential pleiotropy remains a concern in this MR study, despite the lack of evidence from MR-Egger regression and MR-PRESSO methods.…”

Severe, but not moderate asthmatics share blood transcriptomic changes with post-traumatic stress disorder and depression

“…Genome-wide association studies (GWAS) have identified some shared genetic traits between those with asthma and MDD [20,21]. In a cross-trait meta-analysis, Zhu et al, (2019) [20] identified 10 genomic loci shared between asthma and MDD and mendelian randomization identified a significant causal effect of MDD on asthma.…”

“…In a cross-trait meta-analysis, Zhu et al, (2019) [20] identified 10 genomic loci shared between asthma and MDD and mendelian randomization identified a significant causal effect of MDD on asthma. The cross-trait meta-analysis performed by Cao et al, (2021) [21] identified 18 loci jointly associated between MDD and atopic diseases (asthma, eczema, and hay fever). Through Mendelian randomization analysis the investigators found that MDD confers a stronger causal effect on those atopic diseases than they confer on MDD.…”