Mendelian randomization analysis: investigating the causal association between apoptotic proteins and diabetes

Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic impact goal through 2020 and beyond. Circulation. 2010;121:586–613. https://doi.org/10.1161/CIRCULATIONAHA.109.192703.

Article  PubMed  Google Scholar 

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–53. https://doi.org/10.2337/diacare.27.5.1047.

Article  PubMed  Google Scholar 

Kilanowska A, Ziółkowska A. Apoptosis in type 2 diabetes: can it be prevented? Hippo pathway prospects. Int J Mol Sci. 2022;23:636. https://doi.org/10.3390/ijms23020636.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schattenberg JM, Schuchmann M. Diabetes and apoptosis: liver. Apoptosis. 2009;14:1459–71. https://doi.org/10.1007/s10495-009-0366-2.

Article  CAS  PubMed  Google Scholar 

You S, Zheng J, Chen Y, Huang H. Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2022;13:976465. https://doi.org/10.3389/fendo.2022.976465.

Article  PubMed  Google Scholar 

Anuradha R, Saraswati M, Kumar KG, Mary Ann Liebert Inc Publishers. Apoptosis of beta cells in diabetes mellitus. DNA Cell Biol. 2014;33:743–8. https://doi.org/10.1089/dna.2014.2352.

Article  CAS  PubMed  Google Scholar 

Fogarasi M, Dima S. Immunomodulatory functions of TNF-related apoptosis-inducing ligand in type 1 diabetes. Cells. 2024;13:1676. https://doi.org/10.3390/cells13201676.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Laybutt DR, Preston AM, Akerfeldt MC, Kench JG, Busch AK, Biankin AV, et al. Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia. 2007;50:752–63. https://doi.org/10.1007/s00125-006-0590-z.

Article  CAS  PubMed  Google Scholar 

Stankute I, Kazlauskiene M, Blouin J-L, Schwitzgebel VM, Verkauskiene R. Co-segregation analysis and functional trial in vivo of candidate genes for monogenic diabetes. BMJ Open Diabetes Res Care. 2022;10:e003038. https://doi.org/10.1136/bmjdrc-2022-003038.

Article  PubMed  PubMed Central  Google Scholar 

Eizirik DL, Szymczak F, Mallone R. Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes? Nat Rev Endocrinol. 2023;19:425–34. https://doi.org/10.1038/s41574-023-00826-3.

Article  CAS  PubMed  Google Scholar 

Zhang N, Yu H, Liu T, Zhou Z, Feng B, Wang Y, et al. Bmal1 downregulation leads to diabetic cardiomyopathy by promoting Bcl2/IP3R-mediated mitochondrial Ca2 + overload. Redox Biol. 2023;64:102788. https://doi.org/10.1016/j.redox.2023.102788.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Davey Smith G, Ebrahim S. Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22. https://doi.org/10.1093/ije/dyg070.

Article  Google Scholar 

Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Res Synth Methods. 2019;10:486–96. https://doi.org/10.1002/jrsm.1346.

Article  PubMed  PubMed Central  Google Scholar 

Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: the STROBE-MR statement. JAMA. 2021;326:1614–21.

Article  PubMed  Google Scholar 

Sanderson E, Glymour MM, Holmes MV, Kang H, Morrison J, Munafò MR. Mendelian randomization. Nat Rev Methods Primers. 2022. https://doi.org/10.1038/s43586-021-00092-5.

Article  PubMed  PubMed Central  Google Scholar 

Davies NM, Holmes MV, Smith GD. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ Br Med J Publishing Group. 2018;362:k601. https://doi.org/10.1136/bmj.k601.

Article  Google Scholar 

Jiang L, Zheng Z, Fang H, Yang J. A generalized linear mixed model association tool for biobank-scale data. Nat Genet. 2021;53:1616–21. https://doi.org/10.1038/s41588-021-00954-4.

Article  CAS  PubMed  Google Scholar 

Gudjonsson A, Gudmundsdottir V, Axelsson GT, Gudmundsson EF, Jonsson BG, Launer LJ, et al. A genome-wide association study of serum proteins reveals shared loci with common diseases. Nat Commun. 2022;13:480. https://doi.org/10.1038/s41467-021-27850-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Long Y, Tang L, Zhou Y, Zhao S, Zhu H. Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study. BMC Med. 2023;21:66. https://doi.org/10.1186/s12916-023-02761-6.

Article  PubMed  PubMed Central  Google Scholar 

Huang D, Lin S, He J, Wang Q, Zhan Y. Association between COVID-19 and telomere length: A bidirectional Mendelian randomization study. [cited 2025 Oct 1]; https://doi.org/10.1002/jmv.28008

Raghavan NS, Vardarajan B, Mayeux R. Genomic variation in educational attainment modifies Alzheimer disease risk. Neurol Genet. 2019;5:e310. https://doi.org/10.1212/NXG.0000000000000310.

Article  PubMed  PubMed Central  Google Scholar 

Timmers PRHJ, Tiys ES, Sakaue S, Akiyama M, Kiiskinen TTJ, Zhou W, et al. Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging. Nat Aging. 2022;2:19–30. https://doi.org/10.1038/s43587-021-00159-8.

Article  PubMed  Google Scholar 

Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol. 2011;40:740–52.

Article  PubMed  Google Scholar 

Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23:R89–98. https://doi.org/10.1093/hmg/ddu328.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013;178:1177–84.

Article  PubMed  PubMed Central  Google Scholar 

Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40:597–608. https://doi.org/10.1002/gepi.21998.

Article  PubMed  PubMed Central  Google Scholar 

Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46:1985–98. https://doi.org/10.1093/ije/dyx102.

Article  PubMed  PubMed Central  Google Scholar 

Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan NA, Thompson JR. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic. Int J Epidemiol. 2016;45:1961–74. https://doi.org/10.1093/ije/dyw220.

Article  PubMed  PubMed Central  Google Scholar 

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;50:693–8. https://doi.org/10.1038/s41588-018-0099-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L, et al. Cell death modalities: classification and pathophysiological implications. Cell Death Differ. 2007;14:1237–43. https://doi.org/10.1038/sj.cdd.4402148.

Comments (0)

No login
gif