Childhood asthma and type 1 diabetes mellitus: A meta‐analysis and bidirectional Mendelian randomization study

Xie, Junyang; Chen, Gui; Liang, Tianhao; Li, Ang; Liu, Weixing; Wang, Yiyan; Wang, Xiaofen; Kuang, Xiaoxuan; Han, Demin; Liao, Wenjing; Song, Lijuan; Zhang, Xiaowen

doi:10.1111/pai.13858

Cited by 4 publications

(2 citation statements)

References 42 publications

(124 reference statements)

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“…If all instrumental variables related to peripheral blood cells were excluded, the number of instrumental variables would be dramatically reduced. Thus, like other previously published MR studies on asthma ( 46 , 47 ), the SNPs related to peripheral blood cells were not removed from the instrumental variables in our MR study, which could not rule out the potential influence of inflammatory factors on the causal relationship between asthma and epilepsy.…”

Section: Discussionmentioning

confidence: 98%

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Tang

Guo²,

Li³

et al. 2023

Front. Immunol.

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ObjectiveThe relationship between asthma and epilepsy in observational studies is controversial. The purpose of this Mendelian randomization (MR) study is to investigate whether asthma causally contributes to epilepsy susceptibility.MethodsIndependent genetic variants strongly (P<5E-08) associated with asthma were from a recent meta-analysis of genome-wide association studies on 408,442 participants. Two independent summary statistics of epilepsy obtained from the International League Against Epilepsy Consortium (ILAEC, Ncases=15,212, and Ncontrols=29,677) and FinnGen Consortium (Ncases=6,260 and Ncontrols=176,107) were used in the discovery and replication stage, respectively. Several sensitivity analyses and heterogeneity analyses were further conducted to assess the stability of the estimates.ResultsUsing the inverse-variance weighted approach, genetic predisposition to asthma was associated with an elevated risk of epilepsy in the discovery stage (ILAEC: odds ratio [OR]=1.112, 95% confidence intervals [CI]= 1.023-1.209, P = 0.012), but not verified in the replication stage (FinnGen: OR=1.021, 95%CI= 0.896–1.163, P =0.753). However, a further meta-analysis of both ILAEC and FinnGen showed a similar result (OR=1.085, 95% CI: 1.012-1.164, P = 0.022). There were no causal associations between the age onset of asthma and epilepsy. Sensitivity analyses yielded consistent causal estimates.ConclusionThe present MR study suggests that asthma is associated with an increased risk of epilepsy independent of the age onset of asthma. Further studies are warranted to explain the underlying mechanisms of this association.

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Section: Discussionmentioning

confidence: 98%

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Tang

Guo²,

Li³

et al. 2023

Front. Immunol.

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“…Considering the strongest genetic correlation observed among atopic diseases, namely atopic dermatitis, asthma, and allergic rhinitis, as well as their similar associations with autoimmune diseases in observational studies ( 28 – 33 ), we undertook multivariable Mendelian randomization analyses (MVMR1) to examine the potential causal links between these three atopic conditions and six autoimmune diseases. Table S3 provides a detailed breakdown of the instrumental variables employed in these analyses.…”

Section: Methodsmentioning

confidence: 99%

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

Zhou

Cai

et al. 2023

Front. Immunol.

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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.

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No associations between type 1 diabetes and atopic dermatitis, allergic rhinitis, or asthma in childhood: a nationwide Danish case-cohort study

Berg,

Svensson,

Thyssen

et al. 2023

Sci Rep

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Studies examining the association between type 1 diabetes (T1D) and atopic diseases, i.e., atopic dermatitis, allergic rhinitis and asthma have yielded conflicting results due to different algorithms for classification, sample size issues and risk of referral bias of exposed cohorts with frequent contact to health care professionals. Using Danish national registries and well-established disease algorithms, we examined the bidirectional association between T1D and atopic diseases in childhood and adolescence using Cox Proportional Hazard regression compared to two different unexposed cohorts from a population of 1.5 million Danish children born from 1997 to 2018. We found no associations between T1D and atopic dermatitis, allergic rhinitis, or asthma (defined after age five). However, in multivariable analysis we found an increased risk of persistent wheezing (defined as asthma medication before age five) after T1D with an adjusted hazard ratio (aHR) of 1.70 [1.17–2.45]. We also identified an increased risk of developing T1D after persistent wheezing with aHR of 1.24 [1.13–1.36]. This study highlights similar risks of atopic diseases in children with T1D and of T1D in children with atopic disease after age of five years versus healthy controls. However, more research is needed to understand the possible early immunological effects of the link between persistent wheezing and T1D.

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Childhood asthma and type 1 diabetes mellitus: A meta‐analysis and bidirectional Mendelian randomization study

Cited by 4 publications

References 42 publications

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

No associations between type 1 diabetes and atopic dermatitis, allergic rhinitis, or asthma in childhood: a nationwide Danish case-cohort study

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