The role of mitochondria-related proteins in inflammation and autoimmune diseases: a causal analysis using Mendelian randomization and colocalization

Wigerblad G, Kaplan MJ. Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases. Nat Rev Immunol. 2023;23(5):274–88.

Article  Google Scholar 

Davidson A, Diamond B. Autoimmune diseases. N Engl J Med. 2001;345(5):340–50.

Article  Google Scholar 

Cao F, Liu YC, Ni QY, Chen Y, Wan CH, Liu SY, Tao LM, Jiang ZX, Ni J, Pan HF. Temporal trends in the prevalence of autoimmune diseases from 1990 to 2019. Autoimmun Rev. 2023;22(8):103359.

Article  Google Scholar 

Li DP, Han YX, He YS, Wen Y, Liu YC, Fu ZY, Pan HF, Cao F. A global assessment of incidence trends of autoimmune diseases from 1990 to 2019 and predicted changes to 2040. Autoimmun Rev. 2023;22(10):103407.

Article  Google Scholar 

Zhernakova A, Withoff S, Wijmenga C. Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Nat Rev Endocrinol. 2013;9(11):646–59.

Article  Google Scholar 

Miller FW, Alfredsson L, Costenbader KH, Kamen DL, Nelson LM, Norris JM, De Roos AJ. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. J Autoimmun. 2012;39(4):259–71.

Article  Google Scholar 

Hong Y, Wang D, Lin Y, Yang Q, Wang Y, Xie Y, Shu W, Gao S, Hua C. Environmental triggers and future risk of developing autoimmune diseases: molecular mechanism and network toxicology analysis of bisphenol A. Ecotoxicol Environ Saf. 2024;288:117352.

Article  Google Scholar 

Chan DC. Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol. 2020;15:235–59.

Article  Google Scholar 

West AP, Shadel GS. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 2017;17(6):363–75.

Article  Google Scholar 

Zecchini V, Paupe V, Herranz-Montoya I, Janssen J, Wortel IMN, Morris JL, Ferguson A, Chowdury SR, Segarra-Mondejar M, Costa ASH, et al. Fumarate induces vesicular release of mtDNA to drive innate immunity. Nature. 2023;615(7952):499–506.

Article  Google Scholar 

Becker YLC, Duvvuri B, Fortin PR, Lood C, Boilard E. The role of mitochondria in rheumatic diseases. Nat Rev Rheumatol. 2022;18(11):621–40.

Article  Google Scholar 

Gergely P Jr, Grossman C, Niland B, Puskas F, Neupane H, Allam F, Banki K, Phillips PE, Perl A. Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Arthritis Rheum. 2002;46(1):175–90.

Article  Google Scholar 

Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A, Wang K, Zhu J, Yoon HE, Wang X, Kerkhofs M, et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science. 2019;366(6472):1531–6.

Article  Google Scholar 

Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med. 2016;22(2):146–53.

Article  Google Scholar 

Alissafi T, Kalafati L, Lazari M, Filia A, Kloukina I, Manifava M, Lim JH, Alexaki VI, Ktistakis NT, Doskas T, et al. Mitochondrial oxidative damage underlies regulatory T cell defects in autoimmunity. Cell Metab. 2020;32(4):591-604.e597.

Article  Google Scholar 

Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. 2012;337(6098):1062–5.

Article  Google Scholar 

Murphy MP, Hartley RC. Mitochondria as a therapeutic target for common pathologies. Nat Rev Drug Discov. 2018;17(12):865–86.

Article  Google Scholar 

Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA. 2017;318(19):1925–6.

Article  Google Scholar 

Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013;178(7):1177–84.

Article  Google Scholar 

Hong Y, Wang Y, Shu W. Deciphering the genetic underpinnings of neuroticism: a Mendelian randomization study of druggable gene targets. J Affect Disord. 2024;370:147–58.

Article  Google Scholar 

Sheehan NA, Didelez V, Burton PR, Tobin MD. Mendelian randomisation and causal inference in observational epidemiology. PLoS Med. 2008;5(8):e177.

Article  Google Scholar 

Li X, Meng X, Timofeeva M, Tzoulaki I, Tsilidis KK, Ioannidis JP, Campbell H, Theodoratou E. Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. BMJ. 2017;357:j2376.

Article  Google Scholar 

Huang W, Jin T, Zheng W, Yin Q, Yan Q, Pan H, Xu C. Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases. J Autoimmun. 2024;145:103188.

Article  Google Scholar 

Ye J, Richardson TG, McArdle WL, Relton CL, Gillespie KM, Suderman M, Hemani G. Identification of loci where DNA methylation potentially mediates genetic risk of type 1 diabetes. J Autoimmun. 2018;93:66–75.

Article  Google Scholar 

Qian Q, Wu Y, Cui N, Li Y, Zhou Y, Li Y, Lian M, Xiao X, Miao Q, You Z, et al. Epidemiologic and genetic associations between primary biliary cholangitis and extrahepatic rheumatic diseases. J Autoimmun. 2024;148:103289.

Article  Google Scholar 

Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, VanderWeele TJ, Higgins JPT, Timpson NJ, Dimou N, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement. JAMA. 2021;326(16):1614–21.

Article  Google Scholar 

Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021;53(10):1415–24.

Article  Google Scholar 

Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, Ripke S, Lee JC, Jostins L, Shah T, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47(9):979–86.

Article  Google Scholar 

Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996;273(5281):1516–7.

Article  Google Scholar 

Lin YL, Yao T, Wang YW, Lu JH, Chen YM, Wu YQ, Qian XG, Liu JC, Fang LX, Zheng C, et al. Causal association between mitochondrial function and psychiatric disorders: Insights from a bidirectional two-sample Mendelian randomization study. J Affect Disord. 2025;368:55–66.

Article  Google Scholar 

Zhu K, Shi J, Yang R, Zhou C, Liu Z. Evidence based on Mendelian randomization: causal relationship between mitochondrial biological function and lung cancer and its subtypes. Neoplasia. 2023;46:100950.

Article  Google Scholar 

Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65.

Article  Google Scholar 

Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64.

Article  Google Scholar 

Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, Laurin C, Burgess S, Bowden J, Langdon R, et al. The MR-base platform supports systematic causal inference across the human phenome. eLife. 2018;7:e34408.

Article  Google Scholar 

Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, Hartwig FP, Kutalik Z, Holmes MV, Minelli C, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023. Wellcome Open Res. 2019;4:186.

Article  Google Scholar 

Yang Y, Liu W, Zhang Z, Zhang Y, Wang X, Wang J, Cai H, Liu Y, Meng R, Fu Y, et al. Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases. J Autoimmun. 2025;153:103414.

Article  Google Scholar 

Hong K, Hun M, Wu F, Mao J, Wang Y, Zhu J, Zhou X, Xie H, Tian J, Wen C. Association between Omega-3 fatty acids and autoimmune disease: evidence from the umbrella review and Mendelian randomization analysis. Autoimmun Rev. 2024;23(11):103651.

Article  Google Scholar 

Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.

Article  Google Scholar 

Greco MF, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med. 2015;34(21):2926–40.

Article  MathSciNet  Google Scholar 

Burgess S, Dudbridge F, Thompson SG. Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med. 2016;35(11):1880–906.

Article  MathSciNet  Google Scholar 

Hemani G, Bowden J, Davey Smith G. Evaluating the potential role of pleiotropy in Mendelian randomization studies. Hum Mol Genet. 2018;27(R2):r195–208.

Article  Google Scholar 

Giambartolomei C, Vukcevic D, Schadt EE, Franke L, Hingorani AD, Wallace C, Plagnol V. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 2014;10(5):e1004383.

Article  Google Scholar 

Zheng J, Haberland V, Baird D, Walker V, Haycock PC, Hurle MR, Gutteridge A, Erola P, Liu Y, Luo S, et al. Phenome-wide Mendelian randomization map

Comments (0)

No login
gif