Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study
Background: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evalu...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.956850/full |
| _version_ | 1798036404325842944 |
|---|---|
| author | Jian Huang Ying Gui Jing Wu Yubo Xie Yubo Xie |
| author_facet | Jian Huang Ying Gui Jing Wu Yubo Xie Yubo Xie |
| author_sort | Jian Huang |
| collection | DOAJ |
| description | Background: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evaluate the causal effect of AD on ischemic stroke and coronary heart disease.Methods: Twelve single-nucleotide polymorphisms robustly associated with AD (p < 5 × 10–8) were obtained from a genome-wide association study that included 10,788 cases and 30,047 controls by the EArly Genetics and Life course Epidemiology (EAGLE) Consortium (excluding the 23andMe study). The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (122,733 cases and 424,528 controls), and myocardial infarction (43,676 cases and 128,199 controls) were obtained from the MR-Base platform. In the primary MR analyses, we applied the inverse variance weighted method to evaluate the associations. We performed a sensitivity analysis using weighted median, MR-Egger, weighted mode, simple mode, Mendelian Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out methods.Results: In the primary MR analyses, we found no causal association of genetically predicted AD with ischemic stroke [odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.95–1.06], large artery stroke (OR = 1.02, 95% CI: 0.88–1.17), cardioembolic stroke (OR = 1.06, 95% CI: 0.94–1.18), small vessel stroke (OR = 1.05, 95% CI: 0.94–1.17), coronary heart disease (OR = 1.00, 95% CI: 0.94–1.05), and myocardial infarction (OR = 1.03, 95% CI: 0.98–1.09). The results from the primary MR analyses were supported in sensitivity analyses using the weighted median, weighted mode, simple mode, and MR-Egger methods and multivariable MR analyses adjusting for asthma and several traditional risk factors for ischemic stroke and coronary heart disease. MR-Egger intercepts provided no evidence of directional pleiotropy. The MR-PRESSO and leave-one-out analyses did not indicate any outlier instruments.Conclusion: Our MR study does not support a causal association of genetically predicted AD with ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, and myocardial infarction. |
| first_indexed | 2024-04-11T21:12:26Z |
| format | Article |
| id | doaj.art-f22fe86bc02a410393077975834c9cf8 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T21:12:26Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-f22fe86bc02a410393077975834c9cf82022-12-22T04:02:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.956850956850Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization studyJian Huang0Ying Gui1Jing Wu2Yubo Xie3Yubo Xie4Clinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaClinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaClinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaBackground: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evaluate the causal effect of AD on ischemic stroke and coronary heart disease.Methods: Twelve single-nucleotide polymorphisms robustly associated with AD (p < 5 × 10–8) were obtained from a genome-wide association study that included 10,788 cases and 30,047 controls by the EArly Genetics and Life course Epidemiology (EAGLE) Consortium (excluding the 23andMe study). The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (122,733 cases and 424,528 controls), and myocardial infarction (43,676 cases and 128,199 controls) were obtained from the MR-Base platform. In the primary MR analyses, we applied the inverse variance weighted method to evaluate the associations. We performed a sensitivity analysis using weighted median, MR-Egger, weighted mode, simple mode, Mendelian Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out methods.Results: In the primary MR analyses, we found no causal association of genetically predicted AD with ischemic stroke [odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.95–1.06], large artery stroke (OR = 1.02, 95% CI: 0.88–1.17), cardioembolic stroke (OR = 1.06, 95% CI: 0.94–1.18), small vessel stroke (OR = 1.05, 95% CI: 0.94–1.17), coronary heart disease (OR = 1.00, 95% CI: 0.94–1.05), and myocardial infarction (OR = 1.03, 95% CI: 0.98–1.09). The results from the primary MR analyses were supported in sensitivity analyses using the weighted median, weighted mode, simple mode, and MR-Egger methods and multivariable MR analyses adjusting for asthma and several traditional risk factors for ischemic stroke and coronary heart disease. MR-Egger intercepts provided no evidence of directional pleiotropy. The MR-PRESSO and leave-one-out analyses did not indicate any outlier instruments.Conclusion: Our MR study does not support a causal association of genetically predicted AD with ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, and myocardial infarction.https://www.frontiersin.org/articles/10.3389/fgene.2022.956850/fullatopic dermatitisischemic strokecoronary heart diseaseMendelian randomizationmyocardial infarction |
| spellingShingle | Jian Huang Ying Gui Jing Wu Yubo Xie Yubo Xie Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study Frontiers in Genetics atopic dermatitis ischemic stroke coronary heart disease Mendelian randomization myocardial infarction |
| title | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
| title_full | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
| title_fullStr | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
| title_full_unstemmed | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
| title_short | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
| title_sort | investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease a mendelian randomization study |
| topic | atopic dermatitis ischemic stroke coronary heart disease Mendelian randomization myocardial infarction |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.956850/full |
| work_keys_str_mv | AT jianhuang investigatingtheassociationofatopicdermatitiswithischemicstrokeandcoronaryheartdiseaseamendelianrandomizationstudy AT yinggui investigatingtheassociationofatopicdermatitiswithischemicstrokeandcoronaryheartdiseaseamendelianrandomizationstudy AT jingwu investigatingtheassociationofatopicdermatitiswithischemicstrokeandcoronaryheartdiseaseamendelianrandomizationstudy AT yuboxie investigatingtheassociationofatopicdermatitiswithischemicstrokeandcoronaryheartdiseaseamendelianrandomizationstudy AT yuboxie investigatingtheassociationofatopicdermatitiswithischemicstrokeandcoronaryheartdiseaseamendelianrandomizationstudy |