Dataset Information

Association of Atopic Dermatitis with Depression and Suicide: A Two-Sample Mendelian Randomization Study.

ABSTRACT:

Background

Atopic dermatitis (AD) has long been hypothesized to be associated with risk of depression and suicide, but the causal relationship between them is still unclear.

Objective

To evaluate the causality between AD, depression, and suicide using a Mendelian randomization (MR) approach.

Method

We extracted summary-level data for AD, major depression, and suicidal ideation or attempt from published, nonoverlapping genome-wide association studies (GWAS). Inverse variance-weighted (IVW) analysis was used as the primary analysis. Alternate methods, including weighted median, MR Egger, MR pleiotropy residual sum and outlier, weighted mode, and leave-out analysis, were performed to assess pleiotropy.

Results

13 SNPs (13,287 cases and 41,345 controls) were selected as instrumental variables (IVs). The IVW analysis indicated a statistically significant but small causal effect of AD on major depression (OR = 1.027, 95% CI 1.004-1.050; p = 0.020). No significant evidence was observed for a causal effect of AD on suicide. No significant effect of pleiotropy was found.

Conclusion

AD has a significant but small effect on major depression, but not on suicide.

SUBMITTER: Qi HJ

PROVIDER: S-EPMC8831056 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Atopic Dermatitis with Depression and Suicide: A Two-Sample Mendelian Randomization Study.

Qi Hong-Jiao HJ Li Lin-Feng LF

BioMed research international 20220203

<h4>Background</h4>Atopic dermatitis (AD) has long been hypothesized to be associated with risk of depression and suicide, but the causal relationship between them is still unclear.<h4>Objective</h4>To evaluate the causality between AD, depression, and suicide using a Mendelian randomization (MR) approach.<h4>Method</h4>We extracted summary-level data for AD, major depression, and suicidal ideation or attempt from published, nonoverlapping genome-wide association studies (GWAS). Inverse variance ...[more]

PMID: 35155673

Similar Datasets

Project description:BackgroundAccumulating evidence suggests that alterations in gut microbiota composition and diversity are associated with Atopic dermatitis (AD). But until now, the causal association between them has been unclear.MethodsWe employed a two-sample Mendelian Randomization (MR) study to estimate the potential causality of gut microbiota on AD risk. The summary statistics related to the gut microbiota were obtained from a large-scale genome-wide genotype and 16S fecal microbiome dataset from 18,340 individuals (24 cohorts) analyzed by the MiBioGen Consortium, comprising 211 gut microbiota. AD data were also derived from strictly defined AD data collected by FinnGen biobank analysis, which included 218,467 European ancestors (5,321 AD patients and 213,146 controls). The inverse variance weighted method (IVW), weighted median (WME), and MR-Egger were used to determine the changes of AD pathogenic bacterial taxa, followed by sensitivity analysis including horizontal pleiotropy analysis, Cochran's Q test, and the leave-one-out method to assess the reliability of the results. In addition, MR Steiger's test was used to test the suppositional relationship between exposure and outcome.ResultsA total of 2,289 SNPs (p < 1 × 10-5) were included, including 5 taxa and 17 bacterial characteristics (1 phylum, 3 classes, 1 order, 4 families, and 8 genera), after excluding the IVs with linkage disequilibrium (LD). Combining the analysis of the results of the IVW models, there were 6 biological taxa (2 families, and 4 genera) of the intestinal flora positively associated with the risk of AD and 7 biological taxa (1 phylum, 2 classes, 1 order, 1 family, and 2 genera) of the intestinal flora negatively associated. The IVW analysis results showed that Tenericutes, Mollicutes, Clostridia, Bifidobacteriaceae, Bifidobacteriales, Bifidobacterium, and Christensenellaceae R 7 group were negatively correlated with the risk of AD, while Clostridiaceae 1, Bacteroidaceae, Bacteroides, Anaerotruncus, the unknown genus, and Lachnospiraceae UCG001 showed the opposite trend. And the results of the sensitivity analysis were robust. MR Steiger's test showed a potential causal relationship between the above intestinal flora and AD, but not vice versa.ConclusionThe present MR analysis genetically suggests a causal relationship between changes in the abundance of the gut microbiota and AD risk, thus not only providing support for gut microecological therapy of AD but also laying the groundwork for further exploration of the mechanisms by which the gut microbiota contributes to the pathogenesis of AD.

Project description:BackgroundObservational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded.ObjectivesOur study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect.MethodsTwo-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses.ResultsGenetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P<0.001), type 1 diabetes (OR, 1.37; P=0.0084) (ORMVMR1, 1.42; P=0.0155) (ORMVMR2, 1.45; P=0.002), and alopecia areata (OR, 1.98; P=0.0059) (ORMVMR1, 2.55; P<0.001) (ORMVMR2, 1.99; P=0.003) in both univariable and multivariable MR. These causal relationships were supported by sensitivity analyses. No causal effect of AD was identified in relation to systemic lupus erythematosus, vitiligo, and ankylosing spondylitis. Concerning the reverse directions, no significant association was noted.ConclusionThe results of this MR study provide evidence to support the idea that AD causes a greater risk of rheumatoid arthritis, type 1 diabetes and alopecia areata. Further replication in larger samples is needed to validate our findings, and experimental studies are needed to explore the underlying mechanisms of these causal effects.

Project description:BackgroundObservational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety.MethodsBidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (Ncases = 60,653, Ncontrols = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method.ResultsBidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy.ConclusionsOur study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.

Project description:ObjectivesNumerous observational studies have reported associations between circulating cytokines and atopic dermatitis (AD); however, the causal relationships between them remain unclear. To explore the causal correlations and direction of causal effects between AD and levels of 91 circulating cytokines.MethodsTwo-sample Mendelian randomization (MR) analyses were conducted to examine the causal relationships between 91 circulating cytokines and AD using summary statistics from genome-wide association studies (GWAS). Reverse MR analyses were performed to investigate reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Additional transcriptome database and clinical peripheral blood mononuclear cells (PBMCs) samples were utilized to validate the results of MR analyses.ResultsLevels of interleukin (IL)-13, IL-18 Receptor 1, Tumor necrosis factor ligand superfamily member 14 (TNFSF14), TNF-related activation-induced cytokine (TRANCE), C-X-C motif chemokine (CXCL)11, IL-33, TNF-beta and CD5 were suggestively associated with the risk of AD (odds ratio, OR: 1.202, 95% CI: 1.018-1.422, p = 0.030; OR: 1.029, 95% CI: 1.029-1.157, p = 0.004; OR: 1.159, 95% CI: 1.018-1.320, p = 0.026; OR: 1.111, 95% CI: 1.016-1.214, p = 0.020; OR: 0.878, 95% CI: 0.783-0.984, p = 0.025; OR: 0.809, 95% CI: 0.661-0.991, p = 0.041; OR: 0.945, 95% CI: 0.896-0.997, p = 0.038; OR: 0.764, 95% CI: 0.652-0.895, p = 8.26e-04). In addition, levels of cytokines including Axin-1, CXCL5, CXCL10, Oncostatin-M (OSM), Sulfotransferase 1A1 (SULT1A1) and TNFSF14 were suggested to be consequences of AD (Beta: -0.080, p = 0.016; Beta: -0.062, p = 0.036; Beta: -0.066, p = 0.049; Beta: -0.073, p = 0.013; Beta: -0.089, p = 0.008; Beta: -0.079, p = 0.031). IL-13, IL-18R1, TNFSF14, and TRANCE were upregulated in both lesional skin biopsies and PBMCs from AD patients.ConclusionThe study indicates that several cytokines, including IL-13, IL-18R1, TNFSF14, TRANCE, CXCL11, IL-33, TNF-beta, and CD5, are upstream of AD development, whereas a few circulating cytokines are potentially downstream in the development of AD.

Dataset Information

Association of Atopic Dermatitis with Depression and Suicide: A Two-Sample Mendelian Randomization Study.

Background

Objective

Method

Results

Conclusion

Publications

Association of Atopic Dermatitis with Depression and Suicide: A Two-Sample Mendelian Randomization Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets