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. 2023 Jun 15;16(1):132.
doi: 10.1186/s12920-023-01575-y.

Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes

Feiwei Lu  1 , Boting Wu  2 , Yongshi Wang  3   4
Affiliations

Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes

Feiwei Lu et al. BMC Med Genomics. .

Abstract

Background: An association has been indicated between atopic dermatitis (AD), a prevalent chronic inflammatory skin disease, and diabetes mellitus. However, the exact causal relationship between AD and both type 1 diabetes (T1D) and type 2 diabetes (T2D) remains controversial. This study aimed to explore the causal association between AD and diabetes by Mendelian Randomization (MR) approaches.

Methods: Public genetic summary data for AD was obtained from EAGLE study. Single nucleotide polymorphisms of diabetes were retrieved from four genome-wide association studies that had been performed in European populations. Inverse variance weighted (IVW) in MR analysis was used as the primary means of causality estimation. Several complementary analyses and sensitivity analyses were performed to calculate MR estimates and to enhance the causal inference, respectively. The R package 'TwoSampleMR' was used for analysis.

Results: Genetically predicted AD led to a higher risk of T1D (OR, 1.19; 95% CI, 1.05, 1.34; P = 0.006) and T2D (OR, 1.07; 95% CI, 1.02, 1.11; P = 0.003) based on random-effect IVW method. The complementary analyses provided similar positive results. Cochran's Q test and I2 statistics indicated moderate heterogeneity between AD and both T1D and T2D. No significant horizontal pleiotropy was detected by MR-Egger Intercept p except summary data from FinnGen consortium.

Conclusion: Genetically predicted AD is a risk factor for both T1D and T2D. These findings imply potential shared pathological mechanisms between AD and diabetes, thus suggesting the significance of early clinical diagnosis and prevention of AD in reducing the incidence of diabetes.

Keywords: Atopic dermatitis; Genome-wide association study; Mendelian randomization; Type 1 diabetes; Type 2 diabetes.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study design flow diagram of Mendelian randomization (MR). Three key assumptions should be met: Assumption 1: Instrumental variables (IVs) should directly and significantly affect the risk of atopic dermatitis (AD). Assumption 2: IVs associated with any potential confounders should be absolutely avoided. Assumption 3: IVs should only affect type 1 diabetes (T1D) and type 2 diabetes (T2D) through AD. SNPs, single nucleotide polymorphisms
Fig. 2
Fig. 2
Association of genetically predicted AD on the risk of both T1D and T2D. Results were obtained from the inverse variance-weighted method in the random-effects model. AD, atopic dermatitis; T1D, type 1 diabetes; T2D, type 2 diabetes; OR, odds ratio; CI, confidence interval
Fig. 3
Fig. 3
Scatter plot of the MR estimates for the association of AD with the risk of T1D and T2D based on Forgetta et al. (A), FinnGen (B), Mahajan et al. (C) and Xue et al. (D). AD, atopic dermatitis; T1D, type 1 diabetes; T2D, type 2 diabetes; MR-Raps, MR Robust adjusted profile score; MR-PERSSO, MR Pleiotropy Residual Sum and Outlier
Fig. 4
Fig. 4
Leave-one-out plots for the MR analyses of AD on both T1D and T2D based on (A) Forgetta et al., (B) FinnGen, (C) Mahajan et al. and (D) Xue et al. Leave-one-out sensitivity analysis possesses powerful features to detect the bias of any single SNP on MR results. AD, atopic dermatitis; T1D, type 1 diabetes; T2D, type 2 diabetes; SNPs, single nucleotide polymorphisms
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