Mendelian Randomization Indicates That Atopic Dermatitis Contributes to the Occurrence of Diabetes

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2023 Jun 15

PMID 37322504

Authors

Feiwei Lu

Boting Wu

Yongshi Wang

Affiliations

Soon will be listed here.

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 I 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.

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References

Thyssen J, Linneberg A, Carlsen B, Johansen J, Engkilde K, Hansen T . A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study. BMJ Open. 2011; 1(1):e000062. PMC: 3191408. DOI: 10.1136/bmjopen-2011-000062. View

Anderson J, Cornelius J, Jarpe A, Winter W, Peck A . Insulin-dependent diabetes in the NOD mouse model. II. Beta cell destruction in autoimmune diabetes is a TH2 and not a TH1 mediated event. Autoimmunity. 1993; 15(2):113-22. DOI: 10.3109/08916939309043886. View

Norris J, Lee H, Frederiksen B, Erlund I, Uusitalo U, Yang J . Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity. Diabetes. 2017; 67(1):146-154. PMC: 5741144. DOI: 10.2337/db17-0802. View

Verbanck M, Chen C, Neale B, Do R . Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018; 50(5):693-698. PMC: 6083837. DOI: 10.1038/s41588-018-0099-7. View

Drucker A, Wang A, Li W, Sevetson E, Block J, Qureshi A . The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol. 2016; 137(1):26-30. DOI: 10.1016/j.jid.2016.07.012. View

Donath M, Shoelson S . Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011; 11(2):98-107. DOI: 10.1038/nri2925. View

Burgess S, Butterworth A, Thompson S . Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013; 37(7):658-65. PMC: 4377079. DOI: 10.1002/gepi.21758. View

Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan N, Thompson J . A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017; 36(11):1783-1802. PMC: 5434863. DOI: 10.1002/sim.7221. View

. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106(25):3143-421. View

10.

Xue A, Wu Y, Zhu Z, Zhang F, Kemper K, Zheng Z . Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018; 9(1):2941. PMC: 6063971. DOI: 10.1038/s41467-018-04951-w. View

11.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

12.

Wu L, Hwang C, Chung P, Hua T, Chen Y, Chu S . Autoimmune disease comorbidities in patients with atopic dermatitis: a nationwide case-control study in Taiwan. Pediatr Allergy Immunol. 2014; 25(6):586-92. DOI: 10.1111/pai.12274. View

13.

Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan D . Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015; 47(12):1449-1456. PMC: 4753676. DOI: 10.1038/ng.3424. View

14.

Kero J, Gissler M, Hemminki E, Isolauri E . Could TH1 and TH2 diseases coexist? Evaluation of asthma incidence in children with coeliac disease, type 1 diabetes, or rheumatoid arthritis: a register study. J Allergy Clin Immunol. 2001; 108(5):781-3. DOI: 10.1067/mai.2001.119557. View

15.

Shim H, Chasman D, Smith J, Mora S, Ridker P, Nickerson D . A multivariate genome-wide association analysis of 10 LDL subfractions, and their response to statin treatment, in 1868 Caucasians. PLoS One. 2015; 10(4):e0120758. PMC: 4405269. DOI: 10.1371/journal.pone.0120758. View

16.

Imai Y . Interleukin-33 in atopic dermatitis. J Dermatol Sci. 2019; 96(1):2-7. DOI: 10.1016/j.jdermsci.2019.08.006. View

17.

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View

18.

Burgess S, Thompson S . Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017; 32(5):377-389. PMC: 5506233. DOI: 10.1007/s10654-017-0255-x. View

19.

Wang Y, Guo P, Liu L, Zhang Y, Zeng P, Yuan Z . Mendelian Randomization Highlights the Causal Role of Normal Thyroid Function on Blood Lipid Profiles. Endocrinology. 2021; 162(5). DOI: 10.1210/endocr/bqab037. View

20.

Danso M, Boiten W, van Drongelen V, Gmelig Meijling K, Gooris G, El Ghalbzouri A . Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J Dermatol Sci. 2017; 88(1):57-66. DOI: 10.1016/j.jdermsci.2017.05.005. View