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image of Causal Relationship Between Hypertension And Vertigo: A Mendelian Randomization Study

Abstract

Introduction

Current genetic research on the relationship between hypertension and vertigo is limited, and traditional observational studies cannot establish a causal relationship due to design limitations, particularly regarding whether hypertension acts as a causal risk factor for specific vertigo subtypes, such as benign paroxysmal positional vertigo (BPPV).

Methods

This study employed a two-sample MR approach to infer causal relationships genome-wide association study (GWAS) data, thereby addressing the limitations of traditional observational studies. In addition to analyzing the link between total vertigo and hypertension, we examined three major types of vertigo: central vertigo, benign paroxysmal positional vertigo (BPPV), and other peripheral vertigo. The study included 3834 cases of BPPV, 186 cases of central vertigo, 1293 cases of other peripheral vertigo, and 209,582 controls. Various MR methods, including the inverse variance weighted (IVW) approach, MR-Egger, weighted median, and simple mode, were employed to deduce the potential causative associations.

Results

A set of 53 genome-wide significant single-nucleotide polymorphisms (SNPs) associated with hypertension was identified as instrumental variables for subsequent MR analysis. The results indicated a significantly positive correlation between hypertension and the risk of total vertigo (OR: 1.16, 95% CI: 1.08-1.25, <0.05), BPPV (OR: 1.12, CI: 1.01-1.24, and =0.03), and other peripheral vertigo (OR: 1.19, 95% CI: 1.00-1.41, =0.046), whereas no significant association was found with central vertigo (OR: 1.15, 95% CI: 0.74-1.80, =0.53).

Discussion

This study provides genetic evidence for a positive association between hypertension and vertigo, particularly BPPV and peripheral vertigo, but not central vertigo. Hypertension may induce vestibular dysfunction vascular changes leading to tissue hypoxia and cochlear-vestibular degeneration. Limitations include small sample sizes for certain vertigo subtypes (., central vertigo) and limited generalizability to non-European populations.

Conclusion

This MR analysis provides evidence supporting a potential causal relationship between hypertension and an increased risk of certain types of vertigo. These findings contribute to the understanding of risk factors and the early prediction of vertigo.

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2025-09-17
2025-10-30
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References

  1. Macias J.D. Lambert K.M. Massingale S. Ellensohn A. Ann Fritz J. Variables affecting treatment in benign paroxysmal positional vertigo. Laryngoscope 2000 110 11 1921 1924 10.1097/00005537‑200011000‑00029 11081611
    [Google Scholar]
  2. Choi J.Y. Lee E.S. Kim J.S. Vestibular syncope. Curr Opin Neurol 2024 37 1 66 73 10.1097/WCO.0000000000001226 38193502
    [Google Scholar]
  3. Bisdorff A. Vestibular symptoms and history taking. Handb Clin Neurol 2016 137 83 90 10.1016/B978‑0‑444‑63437‑5.00006‑6 27638064
    [Google Scholar]
  4. Ali A.H. Younis N. Abdallah R. Shaer F. Dakroub A. Ayoub M.A. Iratni R. Yassine H.M. Zibara K. Orekhov A. El-Yazbi A.F. Eid A.H. Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 Monoclonal Antibodies. Curr Med Chem 2021 28 36 7427 7445 10.2174/1875533XMTE03NDEo0 33655822
    [Google Scholar]
  5. Pan Q. Li B. Zou K. Zhang J. Wang Y. Tang X. Risk factors and a nomogram model for recurrence of benign paroxysmal positional vertigo: a multicenter cross-sectional study. Front Neurol 2025 16 1542090 10.3389/fneur.2025.1542090 40248016
    [Google Scholar]
  6. Wang L. Cui F. Chen X. Zhang Q. Yang J. Li S. Examining the causal relationship between hypertension and benign paroxysmal vertigo: A univariate and multivariate mendelian randomization study. Acta Otolaryngol 2025 145 5 400 408 10.1080/00016489.2025.2479015 40122118
    [Google Scholar]
  7. Walther L.E. Westhofen M. Presbyvertigo-aging of otoconia and vestibular sensory cells. J Vestib Res 2008 17 2-3 89 92 10.3233/VES‑2007‑172‑303 18413901
    [Google Scholar]
  8. De Stefano A. Dispenza F. Suarez H. Perez-Fernandez N. Manrique-Huarte R. Ban J.H. Kim M.B. Strupp M. Feil K. Oliveira C.A. Sampaio A.L. Araujo M.F.S. Bahmad F. Ganança M.M. Ganança F.F. Dorigueto R. Lee H. Kulamarva G. Mathur N. Di Giovanni P. Petrucci A.G. Staniscia T. Citraro L. Croce A. A multicenter observational study on the role of comorbidities in the recurrent episodes of benign paroxysmal positional vertigo. Auris Nasus Larynx 2014 41 1 31 36 10.1016/j.anl.2013.07.007 23932347
    [Google Scholar]
  9. Tan J. Deng Y. Zhang T. Wang M. Clinical characteristics and treatment outcomes for benign paroxysmal positional vertigo comorbid with hypertension. Acta Otolaryngol 2017 137 5 482 484 10.1080/00016489.2016.1247985 27841099
    [Google Scholar]
  10. Huang X. Zhao J.V. Exploring the pathways linking fasting insulin to coronary artery disease: A proteome-wide Mendelian randomization study. BMC Med 2025 23 1 321 10.1186/s12916‑025‑04127‑6 40442727
    [Google Scholar]
  11. Wang J.L. Zhang P.A. Yuan J. Huang X.C. Cheng J.C. Bao H.J. Li J. Chen S. Causal relationship between 91 circulating inflammatory proteins and gynecological diseases: A two-sample bidirectional Mendelian randomization study. Int J Biol Macromol 2025 316 Pt 1 144729 10.1016/j.ijbiomac.2025.144729 40441565
    [Google Scholar]
  12. Davey Smith G. Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003 32 1 1 22 10.1093/ije/dyg070 12689998
    [Google Scholar]
  13. Wei L. Su R. Luan S. Liao Z. Manavalan B. Zou Q. Shi X. Iterative feature representations improve N4-methylcytosine site prediction. Bioinformatics 2019 35 23 4930 4937 10.1093/bioinformatics/btz408 31099381
    [Google Scholar]
  14. Hasan M.M. Shoombuatong W. Kurata H. Manavalan B. Critical evaluation of web-based DNA N6-methyladenine site prediction tools. Brief Funct Genomics 2021 20 4 258 272 10.1093/bfgp/elaa028 33491072
    [Google Scholar]
  15. Govindaraj RG Subramaniyam S Manavalan B Extremely-randomized-tree-based prediction of n6-methyladenosine sites in saccharomyces cerevisiae. Curr Genomics 2020 21 1 26 33 10.2174/1389202921666200219125625 32655295
    [Google Scholar]
  16. Rosoff D.B. Davey Smith G. Mehta N. Clarke T.K. Lohoff F.W. Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable mendelian randomization study. PLoS Med 2020 17 12 e1003410 10.1371/journal.pmed.1003410 33275596
    [Google Scholar]
  17. Bowden J. Del Greco M F. Minelli C. Davey Smith G. Sheehan N. Thompson J. A framework for the investigation of pleiotropy in two‐sample summary data mendelian randomization. Stat Med 2017 36 11 1783 1802 10.1002/sim.7221 28114746
    [Google Scholar]
  18. Hartwig F.P. Davey Smith G. Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol 2017 46 6 1985 1998 10.1093/ije/dyx102 29040600
    [Google Scholar]
  19. Hemani G. Zheng J. Elsworth B. Wade K.H. Haberland V. Baird D. Laurin C. Burgess S. Bowden J. Langdon R. Tan V.Y. Yarmolinsky J. Shihab H.A. Timpson N.J. Evans D.M. Relton C. Martin R.M. Davey Smith G. Gaunt T.R. Haycock P.C. The MR-Base platform supports systematic causal inference across the human phenome. eLife 2018 7 e34408 10.7554/eLife.34408 29846171
    [Google Scholar]
  20. Burgess S. Thompson S.G. Interpreting findings from mendelian randomization using the MR-Egger method. Eur J Epidemiol 2017 32 5 377 389 10.1007/s10654‑017‑0255‑x 28527048
    [Google Scholar]
  21. Cheng L. Zhao H. Wang P. Zhou W. Luo M. Li T. Han J. Liu S. Jiang Q. Computational methods for identifying similar diseases. Mol Ther Nucleic Acids 2019 18 590 604 10.1016/j.omtn.2019.09.019 31678735
    [Google Scholar]
  22. Krieger J. Frackowiak M. Berger M. Heneka M.T. Jacobs A.H. Falls at advanced age – the importance to search for benign paroxysmal positional vertigo (BPPV). Exp Gerontol 2022 165 111868 10.1016/j.exger.2022.111868 35700849
    [Google Scholar]
  23. Jönsson R. Sixt E. Landahl S. Rosenhall U. Prevalence of dizziness and vertigo in an urban elderly population. J Vestib Res 2004 14 1 47 52 10.3233/VES‑2004‑14105 15156096
    [Google Scholar]
  24. Barin K Dodson EE Dizziness in the elderly. Otolaryngol Clin North Am 2011 44 2 437 454 10.1016/j.otc.2011.01.013
    [Google Scholar]
  25. Ylitörmänen T. Nuotio M.S. Kettunen H. Impinen A. Koivula R. Haikonen K. Trends of fall-related and other fatal injuries in older adults in Finland between 1998 and 2020. Eur J Public Health 2023 33 6 1065 1070 10.1093/eurpub/ckad177 37824274
    [Google Scholar]
  26. Prell T. Finn S. Axer H. How Healthcare Utilization Due to Dizziness and Vertigo Differs Between Older and Younger Adults. Front Med (Lausanne) 2022 9 852187 10.3389/fmed.2022.852187 35252281
    [Google Scholar]
  27. Ganança F.F. Gazzola J.M. Ganança C.F. Caovilla H.H. Ganança M.M. Cruz O.L.M. Elderly falls associated with benign paroxysmal positional vertigo. Rev Bras Otorrinolaringol (Engl Ed) 2010 76 1 113 120 10.1590/S1808‑86942010000100019 20339699
    [Google Scholar]
  28. Jumani K. Powell J. Benign paroxysmal positional vertigo: Management and its impact on falls. Ann Otol Rhinol Laryngol 2017 126 8 602 605 10.1177/0003489417718847 28718303
    [Google Scholar]
  29. Walther L.E. Rogowski M. Schaaf H. Hörmann K. Löhler J. Falls and dizziness in the elderly. Otolaryngol Pol 2010 64 6 354 357 10.1016/S0030‑6657(10)70586‑2 21299055
    [Google Scholar]
  30. Epstein M. Diabetes and hypertension. J Hypertens 1997 15 2 S55 S62 10.1097/00004872‑199715022‑00004 9218200
    [Google Scholar]
  31. Camargo L.L. Rios F.J. Montezano A.C. Touyz R.M. Reactive oxygen species in hypertension. Nat Rev Cardiol 2025 22 1 20 37 10.1038/s41569‑024‑01062‑6 39048744
    [Google Scholar]
  32. Jin X. Xu X. Wang J. Liu X. Deng X. Xie H. Association between hypertension and hearing loss: A systemic review and meta-analysis. Front Neurol 2025 15 1470997 10.3389/fneur.2024.1470997 39839866
    [Google Scholar]
  33. Hara K. Okada M. Takagi D. Tanaka K. Senba H. Teraoka M. Yamada H. Matsuura B. Hato N. Miyake Y. Association between hypertension, dyslipidemia, and diabetes and prevalence of hearing impairment in japan. Hypertens Res 2020 43 9 963 968 10.1038/s41440‑020‑0444‑y 32393863
    [Google Scholar]
  34. Qin P. He C. Ye P. Li Q. Cai C. Li Y. PKCδ regulates the vascular biology in diabetic atherosclerosis. Cell Commun Signal 2023 21 1 330 10.1186/s12964‑023‑01361‑4 37974282
    [Google Scholar]
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