
==== Front
Zhong Nan Da Xue Xue Bao Yi Xue Ban
Zhong Nan Da Xue Xue Bao Yi Xue Ban
zndx
Journal of Central South University Medical Sciences
1672-7347
Central South University Press Xiangya Medical College, 110 Xiangya Road, Changsha City, Hunan Province, China

39311789
1672-7347（2024）06-0932-11
10.11817/j.issn.1672-7347.2024.240103
Articles
Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases
双样本孟德尔随机化分析湿疹与自身免疫性疾病之间的因果关系（英文）http://orcid.org/0000-0002-8881-3916
陈 春里 CHEN Chunli 1
http://orcid.org/0000-0001-7029-6861
闫 思聿 YAN Siyu 1
万 邦贝 WAN Bangbei 2
于杨 依依 YU Yangyiyi 1
曾 金容 ZENG Jinrong 1
http://orcid.org/0000-0001-6313-1217
谭 丽娜 TAN Lina 1
http://orcid.org/0000-0002-4757-6141
鲁 建云 LU Jianyun 1
1 中南大学湘雅三医院皮肤科，长沙 410013
1 Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha 410013
2 海南省妇幼保健中心生殖医学中心，海口 570208
2 Reproductive Medical Center, Hainan Women and Children’s Medical Center, Haikou 570208, China
TIAN Pu english-editor
CHEN Chunli, Email: 1985540159@qq.com, ORCID: 0000-0002-8881-3916

YAN Siyu, Email: sunshine0719happy@163.com, ORCID: 0000-0001-7029-6861

TAN Lina, Email: tanlinawork@163.com, ORCID: 0000-0001-6313-1217
LU Jianyun, Email: xiaoyun3@csu.edu.cn, ORCID: 0000-0002-4757-6141
28 6 2024
49 6 932942
23 2 2024
©Journal of Central South University (Medical Science). All rights reserved.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ (Open access): This is an open access article under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) (https://creativecommons.org/licenses/by-nc-nd/4.0/)。
Objective

The causal relationship between eczema and autoimmune diseases has not been previously reported. This study aims to evaluate the causal relationship between eczema and autoimmune diseases.

Methods

The two‐sample Mendelian randomization (MR) method was used to assess the causal effect of eczema on autoimmune diseases. Summary data from the Genome-Wide Association Study Catalog (GWAS) were obtained from the Integrative Epidemiology Unit (IEU) database. For eczema and autoimmune diseases, genetic instrument variants (GIVs) were identified according to the significant difference (P<5×10-8). Causal effect estimates were generated using the inverse‐variance weighted (IVW) method. MR Egger, maximum likelihood, MR-PRESSO, and MR-RAPS methods were used for alternative analyses. Sensitivity tests, including heterogeneity, horizontal pleiotropy, and leave-one-out analyses, were performed. Finally, reverse causality was assessed.

Results

Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease (OR=1.444, 95% CI 1.199 to 1.738, P<0.001) and ulcerative colitis (OR=1.002, 95% CI 1.001 to 1.003, P=0.002). However, no causal relationship was found for the other 6 autoimmune diseases, including systemic lupus erythematosus (SLE) (OR=0.932, P=0.401), bullous pemphigoid (BP) (OR=1.191, P=0.642), vitiligo (OR=1.000, P=0.327), multiple sclerosis (MS) (OR=1.000, P=0.965), ankylosing spondylitis (AS) (OR=1.001, P=0.121), rheumatoid arthritis (RA) (OR=1.000, P=0.460). Additionally, no reverse causal relationship was found between autoimmune diseases and eczema.

Conclusion

Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis. No causal relationship is found between eczema and SLE, MS, AS, RA, BP, or vitiligo.

目的

湿疹与自身免疫性疾病之间的因果关系尚未见报道。本研究旨在评估湿疹与自身免疫性疾病之间的因果关系。

方法

使用双样本孟德尔随机化(Mendelian randomization，MR)方法来评估湿疹对自身免疫性疾病的因果影响。基因组关联研究(Genome-Wide Association Study Catalog，GWAS)汇总数据来自综合流行病学部门(Integrative Epidemiology Unit，IEU)数据库。根据显著性(P<5×10-8)确定湿疹和自身免疫性疾病的遗传工具变异(genetic instrument variants，GIVs)。使用逆方差加权(inverse‐variance weighted，IVW)方法生成因果效应估计；MR Egger、最大似然、MR-PRESSO和MR-RAPS方法进行替代分析；异质性、水平多效性和留一分析进行敏感性测试。最后评估反向因果关系。

结果

患克罗恩病(Crohn’s disease，CD) (OR=1.444，95% CI 1.199~1.738，P<0.001)和溃疡性结肠炎(ulcerative colitis，UC) (OR=1.002，95% CI 1.001~1.003，P=0.002)的风险随着湿疹的遗传易感性而增加。但其他6种自身免疫性疾病，包括系统性红斑狼疮(systemic lupus erythematosus，SLE) (OR=0.932，P=0.401)、大疱性类天疱疮(bullous pemphigoid，BP) (OR=1.191，P=0.642)、白癜风(OR=1.000，P=0.327)、多发性硬化症(multiple sclerosis，MS) (OR=1.000，P=0.965)、强直性脊柱炎(ankylosing spondylitis，AS) (OR=1.001，P=0.121)和类风湿性关节炎(rheumatoid arthritis，RA) (OR=1.000，P=0.460)与湿疹未见因果关系。同时，自身免疫性疾病与湿疹之间不存在反向因果关系。

结论

湿疹患者患CD和UC的风险更高，而湿疹与SLE、MS、AS、RA、BP和白癜风之间无因果关系。

湿疹
特应性湿疹
自身免疫性疾病
克罗恩病
溃疡性结肠炎
孟德尔随机化
eczema
atopic eczema
autoimmune diseases
Crohn’s disease
ulcerative colitis
Mendelian randomization
the National Natural Science Foundation82273506 82273508 the Hunan Provincial Health Commission Scientific Research Plan ProjectD202304128334
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pmcEczema, sometimes called atopic eczema, is one of the most common chronic, recurrent, itchy inflammation skin diseases with an estimated global prevalence of nearly 230 million [1-3]. Eczema usually starts in infancy, and commonly persists into atopic adulthood[4]. Food allergies, asthma, and allergic rhinitis are all possible complications of eczema[5]. Therefore, eczema is an economic and health burden not only for the patients but also for the whole world. Reported mechanisms included epidermal barrier dysfunction, immune dysregulation, and imbalance of the microbiome, which are mediated by both genetic and environmental factors[6]. Immunologically, eczema is regulated by both T helper 2 (Th2) and T helper 1 (Th1) immune responses during the acute and chronic stages, respectively[7]. At present, eczema is considered as systemic disease that is often developed accompanied by other diseases[8-9]. One study[10] has suggested that atopic eczema is an autoimmune disease. Recent observational studies[8, 11-12] have revealed that eczema is associated with autoimmune diseases like alopecia areata, Crohn’s disease (CD), rheumatoid arthritis (RA), systematic lupus erythematosus (SLE), ulcerative colitis (UC), vitiligo, and other conditions. According to a systematic review[13], atopic eczema patients are also more likely to develop gastrointestinal and skin autoimmune disorders. Autoimmune disorders always occur after the loss of immune tolerance and the subsequent production of autoantibodies[14]. The mechanisms of many autoimmune diseases are also associated with the dysregulation of Th cells. For example, Th2 cells are the major pathogenic cells for RA and SLE[15-16]. Inflammatory bowel disease (IBD) occurs due to the dysregulation of Th1 and Th2 cells, which is similar to atopic eczema[17]. Therefore, it has been speculated that the association between atopic eczema and autoimmune diseases might be positive due to their similar mechanisms of pathogenesis.

However, until now, only some observational or Meta-analysis studies[8, 11-12] have been conducted. In addition, the causal relationship between eczema and autoimmune disorders is still not reported. Observational studies always face some limitations such as selection and recall bias, confounding factors, and reverse causality. Mendelian randomization (MR) can analyze the risk factors of diseases through genetic variants without the influence of confounding factors because alleles are randomly assigned during pregnancy[18]. Therefore, this study aims to use MR analysis to explore the causal association between eczema and autoimmune disorders including rheumatic and immunological diseases [SLE, multiple sclerosis (MS), ankylosing spondylitis (AS), RA, IBD (CD and UC), bullous pemphigoid (BP), and vitiligo] by multiple large-scale Genome-Wide Association Study Catalog (GWAS) datasets.

1 Materials and methods

1.1 Study design and data sources

The overview of the study design is shown in Figure 1. For details, all GWAS summary data were obtained from the IEU Open GWAS database. We only chose the populations of European ancestry to eliminate population stratification bias. The summary statistics for eczema (GWAS ID: ieu-a-996) with a large sample size included 10 788 diagnosed cases and 30 047 controls from the EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium. For MS (GWAS ID: ukb-b-17670), AS (GWAS ID: ukb-b-18194), and RA (GWAS ID: ukb-b-9125), the summary-level statistics were derived from the MRC Integrative Epidemiology Unit (MRC-IEU) including 462 933 subjects. The summary data for CD (GWAS ID: finn-b-K11_CROHN) and BP (GWAS ID: finn-b-L12_PEMPHIGOID_BULL) were obtained from FinnGen, including 212 356 and 218 285 participants, respectively. The summary statistics for UC (GWAS ID: ukb-d-ULCERNAS) and vitiligo (GWAS ID: ukb-a-115) were derived from UK Biobank, including 361 194 and 359 588 Samples, respectively. For SLE (GWAS ID: ebi-a-GCST003156), summary-level statistics were obtained from the discovery cohort of the GWAS, which included 14 267 participants. All appropriate ethical approvals and patient-informed consent were obtained in the original studies.

Figure 1 Study design of MR analyses investigating the causal relationship between eczema and autoimmune diseases

A: Exposures and outcomes of our MR analyses; B: Assumptions of GIVs; C: Directed acyclic graph of the MR framework. MR: Mendelian randomization; SLE: Systemic lupus erythematosus; CD: Crohn’s disease; RA: Rheumatoid arthritis; BP: Bullous pemphigoid; MS: Multiple sclerosis; AS: Ankylosing spondylitis; UC: Ulcerative colitis; GIVs: Genetic instrument variables.

1.2 Selection of the genetic instruments variants

Genetic instruments variants (GIVs) were identified significantly associated with eczema and autoimmune diseases from the GWAS study (P<5×10-8) and removed linkage disequilibrium (LD) (r 2<0.001, 10 000 kb)[19]. All GIVs met the 3 assumptions of MR (Figure 1): 1) Genetic variants were associated with eczema; 2) genetic variants were unassociated with either known or unknown confounders; 3) genetic variants influenced risk of autoimmune diseases through eczema, not through other pathways[19]. MR analyses typically require a threshold of F-statistics>10 to quantify the strength of instrumental variables[19].

1.3 MR analyses

The entire process of the analysis was implemented by R version 4.2. Eczema and autoimmune diseases could be causally linked in a bidirectional manner using the inverse-variance weighted (IVW) method[20-21]. MR Egger[22], maximum likelihood[20], MR-PRESSO[23], and MR-RAPS[24] methods were used for alternative analyses. Forest plots and scatter plots were performed to visualize the analytical results of causal relationship between eczema and autoimmune disorders. The heterogeneity for MR-Egger[22] regression and IVW methods were tested via Cochran’s Q statistics. MR-Egger[22] and MR-PRESSO[23] approaches were conducted to estimate horizontal pleiotropy. The outliers in IVW and MR-Egger regression models were identified using radial MR[19]. The results were checked for the effect of any single nucleotide polymorphism (SNP) using a leave-one-out analysis. The sensitivity analyses of MR were visual for forest plots and scatter plots. In addition, we also made a reverse MR to evaluate the reverse causal relationship.

1.4 Statistical analysis

The two-sample MR and MR-PRESSO packages of R software (ver. 4.3.2) were used for MR analysis. P<0.05 was considered statistically significant.

2 Results

2.1 Causal effect of eczema on autoimmune disorders

We identified GIVs significantly related to eczema (P<5×10-8) and removed LD (r 2<0.001, 10 000 kb). In addition, we also excluded potential confounder-related SNPs. The qualified SNPs were included in the subsequent MR analyses (Supplementary Table 1 and Table 2, https://doi.org/10.57760/sciencedb.xbyxb.00006). The F-statistic values for SNPs of eczema were more than 10 (Table 1). The results of the MR analyses are shown in Table 1, and the visualization through scatter plots and forest plots are presented in Figure 2, respectively. The risk of CD (OR=1.444, 95% CI 1.199 to 1.738, P<0.001) and UC (OR=1.002, 95% CI 1.001 to 1.003, P=0.002) were increased with genetic susceptibility to eczema, according to IVW (Figure 2 and Table 1). However, there was no association between eczema and the other 6 autoimmune diseases, including SLE (OR=0.932, P=0.401), BP (OR=1.191, P=0.642), vitiligo (OR=1.000, P=0.327), MS (OR=1.000, P=0.965), AS (OR=1.001, P=0.121), and RA (OR=1.000, P=0.460; Table 1). In addition, maximum likelihood, MR-PRESSO, and MR-RAPS analyses showed similar results to the IVW method (Figure 2 and Table 2).

Table 1 MR analyses of autoimmune diseases on risk of eczema

Exposure	Outcome	SNP	IVW	Het	Pleio	F	
P	OR (95% CI)	Egger	IVW	Pleio	Egger.intercep	
Eczema	CD	12	<0.001	1.444(1.199-1.738)	0.178	0.148	0.266	0.064	114.749	
UC	12	0.002	1.002(1.001-1.003)	0.027	0.040	0.794	0.000	114.749	
SLE	8	0.401	0.932(0.791-1.098)						
BP	10	0.642	1.191(0.571-2.484)						
Vitiligo	12	0.327	1.000(1.000-1.000)						
MS	7	0.965	1.000(0.999-1.001)						
AS	6	0.121	1.001(1.000-1.002)						
RA	11	0.460	1.000(0.998-1.001)						
MR: Mendelian randomization; SNP: Single nucleotide polymorphism; IVW: Inverse‐variance weighted; OR: Odds ratio; CI: Confidence interval; Het: Heterogeneity; Pleio: Horizontal pleiotropy; CD: Crohn’s disease; UC: Ulcerative colitis; SLE: Systemic lupus erythematosus; BP: Bullous pemphigoid; MS: Multiple sclerosis; AS: Ankylosing spondylitis; RA: Rheumatoid arthritis.

Table 2 Five MR analytical methods for CD and UC on risk of eczema

Exposure	Outcome	Method	SNP	P	OR (95% CI)	
Eczema	CD	MR Egger	12	0.823	0.912(0.416-1.999)	
IVW	12	<0.001	1.444(1.199-1.738)	
Maximum likelihood	12	<0.001	1.459(1.243-1.713)	
MR-PRESSO	12	0.003	1.444(1.137-1.833)	
MR-RAPS	12	<0.001	1.460(1.242-1.715)	
UC	MR Egger	12	0.663	1.001(0.996-1.006)	
IVW	12	0.002	1.002(1.001-1.003)	
Maximum likelihood	12	<0.001	1.002(1.001-1.003)	
MR-PRESSO	12	0.010	1.002(1.000-1.003)	
MR-RAPS	12	<0.001	1.002(1.001-1.003)	
MR: Mendelian randomization; CD: Crohn’s disease; UC: Ulcerative colitis; IVW: Inverse‐variance weighted; SNP: Single nucleotide polymorphism; OR: Odds ratio; CI: Confidence interval.

Figure 2 Forest plots and scatter plots to visualize causal effects of variation in eczema on CD and UC

A and B: Forest plots demonstrate the casual effect of each eczema SNPs for CD (A) and UC (B). C and D: OR and 95% CI correspond to the effects of eczema are presented on CD (C) and UC (D). Total SNP indicates the number of genetic variants used as instruments for MR analysis. E and F: Scatter plots demonstrate the effect of each exposure-associated SNP on CD (E) and UC (F) on the log-odds scale. The slopes of each line represent the causal association for each method. MR: Mendelian randomization; CD: Crohn’s disease; UC: Ulcerative colitis; OR: Odds ratios; CI: Confidence intervals; SNP: Single nucleotide polymorphism; IVW: Inverse variance weighted.

2.2 Sensitivity analyses of MR

Neither heterogeneity nor horizontal pleiotropy were evident in the sensitivity analyses (Table 1). Based on heterogeneity analysis among CD GIVs, Cochran’s Q statistic did not show any significant (P Egger=0.178, P IVW=0.148). For UC, the P values of Cochran’s Q statistic in heterogeneity analysis among GIVs were 0.027 and 0.040 for MR-Egger and IVW, respectively. Meanwhile, the intercept from the MR-Egger regression was 0.0539 (P=0.266) and 0.0003 (P=0.794) for CD and UC, respectively, indicating no horizontal pleiotropy in the GIVs of eczema. MR-PRESSO and MR-Egger test did not reveal any significant outlier SNPs contributing to increased pleiotropy which showed by radial plots (Supplementary Figure 1,https://doi.org/10.57760/sciencedb.xbyxb.00006). The leave-one-out analysis showed no significant single variant driving the causal relationship between eczema and CD or UC (Figure 3), performing by the forest plots (Supplementary Table 3 and Table 4, https://doi.org/10.57760/sciencedb.xbyxb.00006).

Figure 3 Leave-one-out analysis of eczema with the risk of CD (A) and UC (B)

MR: Mendelian randomization; CD: Crohn’s disease; UC: Ulcerative colitis; SNP: Single nucleotide polymorphism.

2.3 Reverse MR analyses

In this reverse MR analyses, no causal relationship was observed between the 8 autoimmune diseases and eczema (Supplementary Table 5, https://doi.org/10.57760/sciencedb.xbyxb.00006). IVW analyses showed no statistically significant for CD, UC, MS, RA, SLE, and vitiligo (all P>0.05). For BP and AS, there were no available SNPs for subsequent MR analysis.

3 Discussion

In this MR study, CD and UC were more likely to develop in patients with eczema. Furthermore, Eczema and SLE, MS, AS, RA, BP, and vitiligo appeared not to be causally associated. There was also no evidence of reverse causality. Several Th1-mediated autoimmune conditions and atopic eczema susceptibility loci overlap in genome-wide association studies[25]. Moreover, although Th2-related cytokines dominated the pathogenesis of acute atopic eczema, Th1 and Th17 lymphocytes were also implicated, especially during chronic atopic eczema[26]. The association between atopic eczema and autoimmune diseases might be explained by these findings, which was most commonly associated with autoimmunity[27]. The relationship between eczema and autoimmune diseases has been described in many observational or Meta-analysis studies. Based on 5 studies[12, 28-31], CD and UC were more prevalent in atopic eczema patients than controls, with pooling OR of 1.66 (P=0.374) and 1.95 (P=0.009), respectively. In addition, according to pooling RR of 1.38 (P=0.426) and 1.49 (P=0.196), atopic eczema patients were also more likely to develop CD and UC than those without the disease[32-34]. A study[35] also showed that children with atopic dermatitis specifically were more likely to develop IBD despite no general association between atopic symptoms and IBD. Findings like these might help identify individuals at risk of IBD. For MS, there was associated with asthma, but not with other Th2-associated diseases (eczema and dermatitis) or any Th1-related disease[36]. Furthermore, a patient treated with dupilumab for atopic eczema was diagnosed with relapsing-remitting MS, but his MS recovered after dupilumab was discontinued and ocrelizumab therapy was started[37]. This may be due to the Th2 suppression and a shift to the Th1/Th17 immune response caused by the dupilumab, which induces the development or progression of Th1/Th17-related diseases, such as psoriasis and MS[38]. For AS, our findings are consistent with previous study[39], which showed no evidence of an association between atopic eczema and AS risk.

On the contrary, some observational studies[12, 31-32] reported that patients with atopic eczema had a higher prevalence of SLE with an OR of 1.74 (P=0.008) and vitiligo with an OR of 4.52 (P<0.001). Similarly, some cohort studies[32, 40-41] showed a higher incidence of SLE and vitiligo in atopic eczema with an average RR of 2.20 (P=0.060) and 1.64 (P=0.207) separately compared with controls. Both the prevalence of RA and the incidence of RA were higher in atopic eczema compared with controls[12, 28, 31-32]. In the largest cohort study[39] of autoimmune comorbidity in children and adults with atopic eczema to date, an increased risk of new-onset RA in the atopic eczema was confirmed as previously, the risk of vitiligo was also found increased. Our results were the opposite. Both atopic eczema and BP are Type 2 immune skin diseases[42]. Atopic eczema increased the risk of developing BP by 76%, which was independent of many BP comorbidities[43]. In addition, a history of atopic eczema or AR would confer increased susceptibility to the development of BP[44]. Therefore, our results were inconsistent with the above studies which concluded eczema could increase the risk of developing RA, SLE, BP, and vitiligo. However, clinical confounders can unavoidably affect both exposure and outcome in observational studies, weakening their accuracy. Although observational studies reported strong correlations, they could not prove a causal link. MR study[18] used genetic variants robustly related to modifiable exposures to understand the influence of the exposure on various outcomes. Genetic variation is passed on randomly from parents to offspring at fertilization, so confounding the factors associated with exposure and outcome could not affect genetic variants. Similarly, genetic variants are generally not influenced by the outcome. MR could be used to explore the association between exposure and outcome, while reducing the potential bias caused by confounding and reverse causation. In addition, the robustness of results has been verified using multiple sensitivity analyses in our MR analysis. Therefore, our MR results are reliable.

Eczema and autoimmune diseases may be related through some mechanisms that have been investigated. Besides eczema, autoimmune diseases may be affected by the same immunologic pathways, especially including the dysregulation of innate and adaptive immunity. Abnormal Th1/Th17 immune responses have been observed both in atopic eczema and several autoimmune diseases (including SLE, IBD, and RA)[45-46]. Another possible explanation is the genetic association. A recent Meta-analysis[47] has identified 10 novel susceptibility loci for atopic eczema related to autoimmune regulation and overlapped with autoimmune diseases by genetically. The risk of developing multiple autoimmune diseases is significantly higher in patients with severe atopic eczema[39]. Atopic diseases and IBD associated genetic variant have been described that affected immune function, barrier function, and cytokine production[48]. Both conditions shared immune dysregulation, with an overactive Th2 response[49-50]. Th2 cells and their associated cytokines, such as interleukin (IL)-4 and IL-13, are elevated due to this immune imbalance, instead of regulatory T cells (Tregs), which suppressed inflammation[51]. Both atopic reactions and intestinal inflammation are linked to these interleukins[51]. They also show impaired epithelial barrier function[52-53]. Monoclonal antibodies targeting specific receptors could treat diseases, potentially involved in common pathology features[50, 54]. Though a possible similar pathophysiological mechanism exists, the causal relationship between eczema with autoimmune diseases has been rarely studied. There might be similarities in therapeutic approaches between autoimmune diseases and atopic eczema by identifying common mechanisms.

Our study has some points of strength. Firstly, with the use of the MR approach, the study is the first time to examine bidirectional causal associations between eczema and autoimmune diseases without being influenced by confounding factors. Secondly, we use 5 analytical methods to perform repeated analyses with consistent results. Thirdly, the reliability and consistency of causal estimation have been proved through sensitivity analysis. However, our study also has some limitations. Researchers have conducted the current study on European ancestry individuals and cannot generalize the results to other races. Then, the OR value is relatively low for some autoimmune disorders, which should be interpreted in caution. Furthermore, despite using strict criteria to identify qualified SNPs to avoid potential confounders and horizontal pleiotropy, we are unable to eliminate horizontal pleiotropy completely because many genetic variants did not have an exact biological function. It is necessary to continue research into the pathway of systemic inflammation contributing to eczema and onset of autoimmune diseases in the future. Additionally, sub-phenotype of eczema which is at greater risk of developing autoimmune disease needs to be identified, along with the effect of systemic anti-inflammatory and biologic treatments for eczema on the severity and risk of autoimmune conditions. Although our results have suggested that there might be a common pathogenetic association between eczema and IBD, more prospective studies are needed to identify the underlying mechanisms of this association. Deeper research will be conducive to the exploration of effective new treatments for both conditions, so as to improve the treatment effect and quality of life of patients.

In summary, this study have suggested that eczema might be causally related to CD and UC, but there is no evidence to support a causal association between eczema and SLE, MS, AS, RA, BP, or vitiligo. Moreover, there is no evidence of reverse causality existing. It is therefore necessary to estimate the risk of autoimmune diseases in patients with eczema (especially those with atopic eczema) to prevent them at an early stage using evidence from observational studies and to increase clinician awareness of the burden of autoimmune comorbidities in patients with eczema.

Funding Statement

This work was supported by the National Natural Science Foundation (82273506, 82273508) and the Hunan Provincial Health Commission Scientific Research Plan Project (D202304128334), China.

Conflict of Interest

The authors declare that they have no conflicts of interest to disclose.

AUTHORS’CONTRIBUTIONS

CHEN Chunli, YAN Siyu, WAN Bangbei Data collection, data analysis, and manuscript drafting; YU Yangyiyi and ZENG Jinrong Data collection and manuscript drafting; TAN Lina and LU Jianyun Study design, manuscript drafting and modifying. All authors read and approved the final manuscript.

Note

http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/202406932.pdf

Ethics approval statement

This study did not require an ethical board approval because it did not contain human or animal trails.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request or the website https://gwas.mrcieu.ac.uk/.

http://dx.chinadoi.cn/10.11817/j.issn.1672-7347.2024.240103
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