Association between Atopic Dermatitis and Major Cardiovascular Outcomes: A Two-Sample Mendelian Randomization Study
Keywords:
Selected:atopic dermatitis, cardiovascular disease, Mendelian randomizationAbstract
Background: Atopic dermatitis (AD) has been linked to cardiovascular disease (CVD) in population-based studies, however, their causal relationship is still unclear.
Objective: To evaluate the causal association of AD with risk of cardiovascular outcomes using a Mendelian randomization (MR) approach.
Method: We extracted summary-level data for AD, stroke, heart failure, coronary artery disease (CAD), myocardial infarction, angina pectoris from published, nonoverlapping genome-wide association studies (GWAS). Inverse variance weighted (IVW) method was used as the primary analysis. Alternative methods, including weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier, weighted mode, and leave-out analysis, were performed to examine potential pleiotropy.
Results: 13 SNPs (13,287 cases and 41,345 controls) were selected as instrumental variables (IVs). No associations of AD with risks of stroke [odds ratio (OR) = 1.03, 95%CI: 0.97-1.09, p = 0.3630], heart failure (OR = 1.04, 95%CI: 0.99-1.09, p= 0.119), coronary artery disease (OR = 1.00, 95%CI: 0.96-1.05, p= 0.988), myocardial infarction (OR = 1.00, 95%CI: 1.00-1.00, p= 0.322), and angina pectoris (OR = 1.00, 95%CI: 1.00-1.00, p= 0.369) was found. No significant effect of pleiotropy was detected.
Conclusions: This MR study does not support a causal effect of AD on stroke, heart failure, CAD, myocardial infarction, angina pectoris.
References
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28. Drucker AM, Qureshi AA, Dummer TJB, Parker L, Li WQ. Atopic dermatitis and risk of hypertension, type 2 diabetes, myocardial infarction and stroke in a cross-sectional analysis from the Canadian Partnership for Tomorrow Project. The British journal of dermatology. 2017;177(4):1043-1051. doi:10.1111/bjd.15727
29. Kwa MC, Silverberg JI. Association Between Inflammatory Skin Disease and Cardiovascular and Cerebrovascular Co-Morbidities in US Adults: Analysis of Nationwide Inpatient Sample Data. American journal of clinical dermatology. 2017;18(6):813-823. doi:10.1007/s40257-017-0293-x
30. Shahjehan RD, Bhutta BS. Coronary Artery Disease. StatPearls. StatPearls Publishing
Copyright © 2021, StatPearls Publishing LLC.; 2021.
31. Rhee T-M, Choi E-K, Han K-D, Lee S-R, Oh S. Impact of the Combinations of Allergic Diseases on Myocardial Infarction and Mortality. The journal of allergy and clinical immunology In practice. 2021;9(2)doi:10.1016/j.jaip.2020.09.008
2. Bylund S, von Kobyletzki LB, Svalstedt M, Svensson A. Prevalence and Incidence of Atopic Dermatitis: A Systematic Review. Acta Derm Venereol. Jun 9 2020;100(12):adv00160. doi:10.2340/00015555-3510
3. Sacotte R, Silverberg JI. Epidemiology of adult atopic dermatitis. Clinics in dermatology. 2018;36(5):595-605. doi:10.1016/j.clindermatol.2018.05.007
4. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. The Lancet. 2020;396(10247):345-360. doi:10.1016/s0140-6736(20)31286-1
5. Drucker AM, Wang AR, Li W-Q, Sevetson E, Block JK, Qureshi AA. The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. The Journal of investigative dermatology. 2017;137(1):26-30. doi:10.1016/j.jid.2016.07.012
6. Smith GD, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? International journal of epidemiology. 2003;32(1):1-22.
7. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. Apr 15 2008;27(8):1133-63. doi:10.1002/sim.3034
8. Katikireddi SV, Green MJ, Taylor AE, Davey Smith G, Munafò MR. Assessing causal relationships using genetic proxies for exposures: an introduction to Mendelian randomization. Addiction. 2018;113(4):764-774. doi:10.1111/add.14038
9. Au Yeung SL, Jiang CQ, Cheng KK, et al. Evaluation of moderate alcohol use and cognitive function among men using a Mendelian randomization design in the Guangzhou biobank cohort study. Am J Epidemiol. 2012;175(10):1021-1028. doi:10.1093/aje/kwr462
10. Didelez V, Sheehan N. Mendelian randomization as an instrumental variable approach to causal inference. Stat Methods Med Res. 2007;16(4):309-330.
11. Paternoster L, Standl M, Waage J, et al. 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. doi:10.1038/ng.3424
12. Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018;50(4):524-537. doi:10.1038/s41588-018-0058-3
13. Shah S, Henry A, Roselli C, et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat Commun. 2020;11(1):163. doi:10.1038/s41467-019-13690-5
14. Nelson CP, Goel A, Butterworth AS, et al. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat Genet. 2017;49(9):1385-1391. doi:10.1038/ng.3913
15. Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016;40(4):304-314. doi:10.1002/gepi.21965
16. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. International journal of epidemiology. 2015;44(2):512-525. doi:10.1093/ije/dyv080
17. Wootton RE, Lawn RB, Millard LAC, et al. Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study. BMJ. Sep 25 2018;362:k3788. doi:10.1136/bmj.k3788
18. Verbanck M, Chen C-Y, 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. doi:10.1038/s41588-018-0099-7
19. Andersen YMF, Egeberg A, Gislason GH, Hansen PR, Skov L, Thyssen JP. Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis. The Journal of allergy and clinical immunology. 2016;138(1)doi:10.1016/j.jaci.2016.01.015
20. Drucker AM, Li WQ, Cho E, et al. Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women. Allergy. 2016;71(10):1496-1500. doi:10.1111/all.12957
21. Ivert LU, Johansson EK, Dal H, Lindelöf B, Wahlgren C-F, Bradley M. Association Between Atopic Dermatitis and Cardiovascular Disease: A Nationwide Register-based Case-control Study from Sweden. Acta dermato-venereologica. 2019;99(10):865-870. doi:10.2340/00015555-3235
22. Shalom G, Dreiher J, Kridin K, et al. Atopic dermatitis and the metabolic syndrome: a cross-sectional study of 116 816 patients. Journal of the European Academy of Dermatology and Venereology : JEADV. 2019;33(9):1762-1767. doi:10.1111/jdv.15642
23. Silverberg JI. Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population-based studies. Allergy. 2015;70(10):1300-1308. doi:10.1111/all.12685
24. Silverwood RJ, Forbes HJ, Abuabara K, et al. Severe and predominantly active atopic eczema in adulthood and long term risk of cardiovascular disease: population based cohort study. BMJ (Clinical research ed). 2018;361:k1786. doi:10.1136/bmj.k1786
25. Jachiet M, Nosbaum A, Staumont-Sallé D, et al. Low cardiovascular risk and poor quality of life associated with tobacco use and skin infections in adult atopic dermatitis: result of a French multicenter study. Journal of the European Academy of Dermatology and Venereology : JEADV. 2019;33(12):e451-e453. doi:10.1111/jdv.15774
26. Standl M, Tesch F, Baurecht H, et al. Association of Atopic Dermatitis with Cardiovascular Risk Factors and Diseases. The Journal of investigative dermatology. 2017;137(5):1074-1081. doi:10.1016/j.jid.2016.11.031
27. Treudler R, Zeynalova S, Walther F, Engel C, Simon JC. Atopic dermatitis is associated with autoimmune but not with cardiovascular comorbidities in a random sample of the general population in Leipzig, Germany. Journal of the European Academy of Dermatology and Venereology : JEADV. 2018;32(2):e44-e46. doi:10.1111/jdv.14495
28. Drucker AM, Qureshi AA, Dummer TJB, Parker L, Li WQ. Atopic dermatitis and risk of hypertension, type 2 diabetes, myocardial infarction and stroke in a cross-sectional analysis from the Canadian Partnership for Tomorrow Project. The British journal of dermatology. 2017;177(4):1043-1051. doi:10.1111/bjd.15727
29. Kwa MC, Silverberg JI. Association Between Inflammatory Skin Disease and Cardiovascular and Cerebrovascular Co-Morbidities in US Adults: Analysis of Nationwide Inpatient Sample Data. American journal of clinical dermatology. 2017;18(6):813-823. doi:10.1007/s40257-017-0293-x
30. Shahjehan RD, Bhutta BS. Coronary Artery Disease. StatPearls. StatPearls Publishing
Copyright © 2021, StatPearls Publishing LLC.; 2021.
31. Rhee T-M, Choi E-K, Han K-D, Lee S-R, Oh S. Impact of the Combinations of Allergic Diseases on Myocardial Infarction and Mortality. The journal of allergy and clinical immunology In practice. 2021;9(2)doi:10.1016/j.jaip.2020.09.008
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2022-10-31
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Copyright (c) 2022 Hongjiao Qi, Lifeng Wang, Linfeng Li
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Qi H, Wang L, Li L. Association between Atopic Dermatitis and Major Cardiovascular Outcomes: A Two-Sample Mendelian Randomization Study. Dermatol Pract Concept. 2022;12(4):e2022165. doi:10.5826/dpc.1204a165
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