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An Exploratory Analysis of Essential Tremor and Associated Phenotypes Cover

An Exploratory Analysis of Essential Tremor and Associated Phenotypes

Open Access
|Apr 2026

References

  1. Song P, Zhang Y, Zha M, Yang Q, Ye X, Yi Q, et al. The global prevalence of essential tremor, with emphasis on age and sex: A meta-analysis. J Glob Health. 2021;11:04028. DOI: 10.7189/jogh.11.04028
  2. Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Movement Disorders. 2018;33(1):7587. DOI: 10.1002/mds.27121
  3. Hopfner F, Helmich RC. The etiology of essential tremor: Genes versus environment. Parkinsonism Relat Disord. 2018;46 Suppl 1:S92S96. DOI: 10.1016/j.parkreldis.2017.07.014
  4. Dai D, Samiian A, Fernandes J, Coetzer H. Multiple Comorbidities, Psychiatric Disorders, Healthcare Resource Utilization and Costs Among Adults with Essential Tremor: A Retrospective Observational Study in a Large US Commercially Insured and Medicare Advantage Population. J Health Econ Outcomes Res. 2022;9(2):3746. DOI: 10.36469/jheor.2022.37307
  5. Liao C, Castonguay C-E, Heilbron K, Vuokila V, Medeiros M, Houle G, et al. Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis. JAMA Neurology. 2022;79(2):185193. DOI: 10.1001/jamaneurol.2021.4781
  6. Skuladottir AT, Stefansdottir L, Halldorsson GH, Stefansson OA, Bjornsdottir A, Jonsson P, et al. GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis. Communications Biology. 2024;7(1):504. DOI: 10.1038/s42003-024-06207-4
  7. Handforth A, Parker GA. Conditions Associated with Essential Tremor in Veterans: A Potential Role for Chronic Stress. Tremor Other Hyperkinet Mov (N Y). 2018;8:517. DOI: 10.5334/tohm.400
  8. Louis ED. Essential tremor as a neuropsychiatric disorder. Journal of the Neurological Sciences. 2010;289(1):144148. DOI: 10.1016/j.jns.2009.08.029
  9. Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, Agundez JAG. Sleep disorders in essential tremor: systematic review and meta-analysis. Sleep. 2020;43(9). DOI: 10.1093/sleep/zsaa039
  10. Chandran V, Pal PK, Reddy JYC, Thennarasu K, Yadav R, Shivashankar N. Non-motor features in essential tremor. Acta Neurologica Scandinavica. 2012;125(5):332337. DOI: 10.1111/j.1600-0404.2011.01573.x
  11. Kim J-S, Song I-U, Shim Y-S, Park J-W, Yoo J-Y, Kim Y-I, Lee K-S, et al. Cognitive Impairment in Essential Tremor without Dementia. Journal of Clinical Neurology. 2009(1738–6586 (Print)). DOI: 10.3988/jcn.2009.5.2.81
  12. Ong YL, Deng X, Tan EK. Etiologic links between environmental and lifestyle factors and Essential tremor. Ann Clin Transl Neurol. 2019;6(5):979989. DOI: 10.1002/acn3.758
  13. Prakash KM, Fook-Choong S, Yuen Y, Tan EK. Exploring the relationship between caffeine intake and essential tremor. Journal of the Neurological Sciences. 2006;251(1):98101. DOI: 10.1016/j.jns.2006.09.007
  14. Louis ED, Jurewicz EC, Applegate L, Luchsinger JA, Factor-Litvak P, Parides M. Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls. Mov Disord. 2004;19(5):499504. DOI: 10.1002/mds.20035
  15. Nicoletti A, Mostile G, Cappellani R, Contrafatto D, Arabia G, Lamberti P, et al. Wine drinking and essential tremor: a possible protective role. Mov Disord. 2011;26(7):13101315. DOI: 10.1002/mds.23603
  16. Louis ED, Michalec M. Semi-quantitative data on ethanol consumption in 354 ET cases and 370 controls. J Neurol Sci. 2014;347(1–2):174178. DOI: 10.1016/j.jns.2014.09.042
  17. Louis ED, Benito-Leon J, Bermejo-Pareja F. Population-based study of baseline ethanol consumption and risk of incident essential tremor. J Neurol Neurosurg Psychiatry. 2009;80(5):494497. DOI: 10.1136/jnnp.2008.162701
  18. Jimenez-Jimenez FJ, de Toledo-Heras M, Alonso-Navarro H, Ayuso-Peralta L, Arevalo-Serrano J, Ballesteros-Barranco A, et al. Environmental risk factors for essential tremor. Eur Neurol. 2007;58(2):106113. DOI: 10.1159/000103646
  19. Louis ED, Zheng W, Jurewicz EC, Watner D, Chen J, Factor-Litvak P, et al. Elevation of blood beta-carboline alkaloids in essential tremor. Neurology. 2002;59(12):19401944. DOI: 10.1212/01.WNL.0000038385.60538.19
  20. Louis ED, Jiang W, Pellegrino KM, Rios E, Factor-Litvak P, Henchcliffe C, et al. Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor. Neurotoxicology. 2008;29(2):294300. DOI: 10.1016/j.neuro.2007.12.001
  21. Louis ED, Benito-Leon J, Moreno-Garcia S, Vega S, Romero JP, Bermejo-Pareja F, et al. Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in essential tremor cases in Spain. Neurotoxicology. 2013;34:264268. DOI: 10.1016/j.neuro.2012.09.004
  22. Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P. Blood harmane concentrations and dietary protein consumption in essential tremor. Neurology. 2005;65(3):391396. DOI: 10.1212/01.wnl.0000172352.88359.2d
  23. Benito-León J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain Study G. Population-based case–control study of cigarette smoking and essential tremor. Movement Disorders. 2008;23(2):246252. DOI: 10.1002/mds.21810
  24. Louis ED, Benito-Leon J, Bermejo-Pareja F, Neurological Disorders in Central Spain Study G. Population-based prospective study of cigarette smoking and risk of incident essential tremor. Neurology. 2008;70(19):16821687. DOI: 10.1212/01.wnl.0000311271.42596.32
  25. Homann CN, Ivanic G, Homann B, Purkart TU. Vitamin D and Hyperkinetic Movement Disorders: A Systematic Review. Tremor Other Hyperkinet Mov (N Y). 2020.10:32. DOI: 10.5334/tohm.74
  26. Sazci A, Uren N, Idrisoglu HA, Ergul E. The rs2228570 Variant of the Vitamin D Receptor Gene is Associated with Essential Tremor. Neuroscience Bulletin. 2019;35(2):362364. DOI: 10.1007/s12264-018-0287-6
  27. Yilmaz NH, Akbostanci MC, Yılmaz N. Sensorineural Hearing Loss in Non-depressed Essential Tremor Cases and Controls: A Clinical and Audiometric Study. Tremor Other Hyperkinet Mov (N Y). 2015.5:281. DOI: 10.5334/tohm.237
  28. Ondo WG, Sutton L, Dat Vuong K, Lai D, Jankovic J. Hearing impairment in essential tremor. Neurology. 2003;61(8):10931097. DOI: 10.1212/01.WNL.0000086376.40750.AF
  29. Hu T, Guralnik JM, Yao L, Gustat J, Harville EW, Webber LS, et al. Postural hand tremor and incident hypertension in young to middle-aged adults: the Bogalusa heart study. J Hypertens. 2016;34(7):12731278. DOI: 10.1097/HJH.0000000000000963
  30. Ross JP, Mohtashami S, Leveille E, Johnson AM, Xiong L, Dion PA, et al. Association study of essential tremor genetic loci in Parkinson’s disease. Neurobiology of Aging. 2018;66:178.e13178.e15. DOI: 10.1016/j.neurobiolaging.2018.01.001
  31. Yoo S-W, Ha S, Lyoo CH, Kim Y, Yoo J-Y, Kim J-S. Exploring the link between essential tremor and Parkinson’s disease. npj Parkinson’s Disease. 2023;9(1):134. DOI: 10.1038/s41531-023-00577-y
  32. Thenganatt MA, Jankovic J. The relationship between essential tremor and Parkinson’s disease. Parkinsonism & Related Disorders. 2016;22:S162S165. DOI: 10.1016/j.parkreldis.2015.09.032
  33. Benito-Leon J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain Study G. Risk of incident Parkinson’s disease and parkinsonism in essential tremor: a population based study. J Neurol Neurosurg Psychiatry. 2009;80(4):423425. DOI: 10.1136/jnnp.2008.147223
  34. Jain S, Lo SE, Louis ED. Common misdiagnosis of a common neurological disorder: how are we misdiagnosing essential tremor? Arch Neurol. 2006;63(8):11001104. DOI: 10.1001/archneur.63.8.1100
  35. Hemani G, Tilling K, Davey Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLOS Genetics. 2017;13(11):e1007081. DOI: 10.1371/journal.pgen.1007081
  36. Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. eLife. 2018;7:e34408. DOI: 10.7554/eLife.34408
  37. Phan L, Zhang H, Wang Q, Villamarin R, Hefferon T, Ramanathan A, et al. The evolution of dbSNP: 25 years of impact in genomic research. Nucleic Acids Res. 2025;53(D1):D925D931. DOI: 10.1093/nar/gkae977
  38. Grotzinger AD, Rhemtulla M, de Vlaming R, Ritchie SJ, Mallard TT, Hill WD, et al. Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nature Human Behaviour. 2019;3(5):513525. DOI: 10.1038/s41562-019-0566-x
  39. Bowden J, Del Greco MF, Minelli C, Zhao Q, Lawlor DA, Sheehan NA, et al. Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption. Int J Epidemiol. 2019;48(3):728742. DOI: 10.1093/ije/dyy258
  40. Burgess S, Butterworth A, Thompson SG. Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data. Genetic Epidemiology. 2013;37(7):658665. DOI: 10.1002/gepi.21758
  41. Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants. Epidemiology. 2017;28(1):3042. DOI: 10.1097/EDE.0000000000000559
  42. Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. International Journal of Epidemiology. 2017;46(6):19851998. DOI: 10.1093/ije/dyx102
  43. Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755764. DOI: 10.1093/ije/dyr036
  44. 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. Nature Genetics. 2018;50(5):693698. DOI: 10.1038/s41588-018-0099-7
  45. Bland JM, Altman DG. Multiple significance tests: the Bonferroni method. BMJ. 1995;310(6973):170. DOI: 10.1136/bmj.310.6973.170
  46. von Berg J, ten Dam M, van der Laan SW, de Ridder J. PolarMorphism enables discovery of shared genetic variants across multiple traits from GWAS summary statistics. Bioinformatics. 2022;38(Supplement_1):i212i219. DOI: 10.1093/bioinformatics/btac228
  47. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013;14:128. DOI: 10.1186/1471-2105-14-128
  48. Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(W1):W90W97. DOI: 10.1093/nar/gkw377
  49. Xie Z, Bailey A, Kuleshov MV, Clarke DJB, Evangelista JE, Jenkins SL, et al. Gene Set Knowledge Discovery with Enrichr. Current Protocols. 2021;1(3):e90. DOI: 10.1002/cpz1.90
  50. Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Patterson N, et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics. 2015;47(3):291295. DOI: 10.1038/ng.3211
  51. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617627. DOI: 10.1001/archpsyc.62.6.617
  52. Carthy ER. Autonomic dysfunction in essential hypertension: A systematic review. Annals of Medicine and Surgery. 2014;3(1):27. DOI: 10.1016/j.amsu.2013.11.002
  53. Haile LM, Kamenov K, Briant PS, Orji AU, Steinmetz JD, Abdoli A, et al. Hearing loss prevalence and years lived with disability, 1990–2019: findings from the Global Burden of Disease Study 2019. The Lancet. 2021;397(10278):9961009. DOI: 10.1016/S0140-6736(21)00516-X
  54. Roth T. Insomnia: Definition, Prevalence, Etiology, and Consequences. Journal of Clinical Sleep Medicine. 2007;3(5 suppl):S7S10. DOI: 10.5664/jcsm.26929
  55. 2021 NSDUH Annual National Report. In: Administration SAaMHS, editor. 2021.
  56. Willis AW, Roberts E, Beck JC, Fiske B, Ross W, Savica R, et al. Incidence of Parkinson disease in North America. npj Parkinson’s Disease. 2022;8(1):170. DOI: 10.1038/s41531-022-00410-y
  57. Auton A, Abecasis GR, Altshuler DM, Durbin RM, Abecasis GR, Bentley DR, et al. A global reference for human genetic variation. Nature. 2015;526(7571):6874. DOI: 10.1038/nature15393
  58. Team RC. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2025.
  59. Xia Y, Yang Y. RMSEA, CFI, and TLI in structural equation modeling with ordered categorical data: The story they tell depends on the estimation methods. Behavior Research Methods. 2019;51(1):409428. DOI: 10.3758/s13428-018-1055-2
  60. Pavlov G, Maydeu-Olivares A, Shi D. Using the Standardized Root Mean Squared Residual (SRMR) to Assess Exact Fit in Structural Equation Models. Educ Psychol Meas. 2021;81(1):110130. DOI: 10.1177/0013164420926231
  61. Zeng S, Zhou X, He R, Zhao Y, Liu Z, Xu Q, et al. Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson’s Disease. Tremor Other Hyperkinet Mov (N Y). 2024;14:25. DOI: 10.5334/tohm.885
  62. Li M, Zhao Y, Wang Y, He R, Zhao G, Wang X, et al. Genetic Variation Analysis of Essential Tremor: Insights from the China Essential Tremor Alliance Cohort. Mov Disord. 2025. DOI: 10.1002/mds.70106
  63. Louis ED. Increased Medical Comorbidities in Essential Tremor-A Wake-up Call? J Health Econ Outcomes Res. 2022;9(2):123124. DOI: 10.36469/001c.38905
  64. Mullins N, Forstner AJ, O’Connell KS, Coombes B, Coleman JRI, Qiao Z, et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics. 2021;53(6):817829. DOI: 10.1038/s41588-021-00857-4
  65. Saunders GRB, Wang X, Chen F, Jang S-K, Liu M, Wang C, et al. Genetic diversity fuels gene discovery for tobacco and alcohol use. Nature. 2022;612(7941):720724. DOI: 10.1038/s41586-022-05477-4
  66. Watanabe K, Stringer S, Frei O, Umićević Mirkov M, de Leeuw C, Polderman TJC, et al. A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet. 2019;51(9):13391348. DOI: 10.1038/s41588-019-0481-0
  67. Li M, Dang X, Chen Y, Chen Z, Xu X, Zhao Z, et al. Cognitive processing speed and accuracy are intrinsically different in genetic architecture and brain phenotypes. Nat Commun. 2024;15(1):7786. DOI: 10.1038/s41467-024-52222-8
  68. Watanabe K, Jansen PR, Savage JE, Nandakumar P, Wang X, Agee M, et al. Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways. Nature Genetics. 2022;54(8):11251132. DOI: 10.1038/s41588-022-01124-w
  69. Graham SE, Clarke SL, Wu K-HH, Kanoni S, Zajac GJM, Ramdas S, et al. The power of genetic diversity in genome-wide association studies of lipids. Nature. 2021;600(7890):675679. DOI: 10.1038/s41586-021-04064-3
  70. Howard DM, Adams MJ, Clarke T-K, Hafferty JD, Gibson J, Shirali M, et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience. 2019;22(3):343352. DOI: 10.1038/s41593-018-0326-7
  71. Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. The Lancet Neurology. 2019;18(12):10911102. DOI: 10.1016/S1474-4422(19)30320-5
  72. Wang X, Hivert V, Groot S, Wang Y, Yengo L, McGrath JJ, et al. Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D. PLOS Genetics. 2023;19(11):e1011033. DOI: 10.1371/journal.pgen.1011033
DOI: https://doi.org/10.5334/tohm.1168 | Journal eISSN: 2160-8288
Language: English
Page range: 27 - 27
Submitted on: Jan 19, 2026
Accepted on: Apr 9, 2026
Published on: Apr 28, 2026
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2026 Dylan Gharibian, Miranda Medeiros, Patrick A. Dion, Guy A. Rouleau, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.