دورية أكاديمية
Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation.
| العنوان: | Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation. |
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| المؤلفون: | Juvinao-Quintero, DL, Sharp, GC, Sanderson, ECM, Relton, CL, Elliott, HR |
| بيانات النشر: | Springer |
| سنة النشر: | 2023 |
| المجموعة: | University of Exeter: Open Research Exeter (ORE) |
| مصطلحات موضوعية: | Causality, DNA methylation, Epigenetics, Mendelian randomisation, Type 2 diabetes |
| الوصف: | This is the final version. Available from Springer via the DOI in this record. ; Data availability: ALSPAC data used for this submission will be made available on request to the ALSPAC executive committee (ALSPACexec@bristol.ac.uk). The ALSPAC data management plan (available at www.bristol.ac.uk/alspac/researchers/access/) describes in detail the policy regarding data sharing, which takes place through a system of managed open access. ; AIMS/HYPOTHESIS: Several studies have identified associations between type 2 diabetes and DNA methylation (DNAm). However, the causal role of these associations remains unclear. This study aimed to provide evidence for a causal relationship between DNAm and type 2 diabetes. METHODS: We used bidirectional two-sample Mendelian randomisation (2SMR) to evaluate causality at 58 CpG sites previously detected in a meta-analysis of epigenome-wide association studies (meta-EWAS) of prevalent type 2 diabetes in European populations. We retrieved genetic proxies for type 2 diabetes and DNAm from the largest genome-wide association study (GWAS) available. We also used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) when associations of interest were not available in the larger datasets. We identified 62 independent SNPs as proxies for type 2 diabetes, and 39 methylation quantitative trait loci as proxies for 30 of the 58 type 2 diabetes-related CpGs. We applied the Bonferroni correction for multiple testing and inferred causality based on p<0.001 for the type 2 diabetes to DNAm direction and p<0.002 for the opposing DNAm to type 2 diabetes direction in the 2SMR analysis. RESULTS: We found strong evidence of a causal effect of DNAm at cg25536676 (DHCR24) on type 2 diabetes. An increase in transformed residuals of DNAm at this site was associated with a 43% (OR 1.43, 95% CI 1.15, 1.78, p=0.001) higher risk of type 2 diabetes. We inferred a likely causal direction for the remaining CpG sites assessed. In silico analyses showed that the CpGs analysed were ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1247-1259; Print-Electronic |
| اللغة: | English |
| تدمد: | 0012-186X 1432-0428 |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pubmed/37202507Test; https://www.bristol.ac.uk/alspac/researchers/accessTest/; Diabetologia, 66(7); orcid:0000-0003-2906-4035 (Sharp, Gemma C); ScopusID: 56898577600 (Sharp, Gemma C); Vol. 66, No. 7, pp. 1247-1259; https://doi.org/10.1007/s00125-023-05914-7Test; MC_UU_00011/5; MC_UU_00011/1; 217065/Z/19/Z; http://hdl.handle.net/10871/134375Test; Diabetologia |
| DOI: | 10.1007/s00125-023-05914-7 |
| الإتاحة: | https://doi.org/10.1007/s00125-023-05914-7Test http://hdl.handle.net/10871/134375Test |
| حقوق: | © The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0Test/. ; https://creativecommons.org/licenses/by/4.0Test/ ; CC BY |
| رقم الانضمام: | edsbas.7B03491 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 0012186X 14320428 |
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| DOI: | 10.1007/s00125-023-05914-7 |