Hostname: page-component-848d4c4894-2pzkn Total loading time: 0 Render date: 2024-05-24T05:14:25.770Z Has data issue: false hasContentIssue false

Association Between Dysmenorrhea and Risk of Epilepsy in East Asian Populations: A Bidirectional Two-Sample Mendelian Randomization Study

Published online by Cambridge University Press:  15 December 2023

Yuehan Ren
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Junning Zhang
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Oncology of Integrative Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
Tong Chen
Affiliation:
Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Jiaqin Chen
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
Yan Liao
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Tingxiu Liu
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Liangliang Yang
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Chang Liu
Affiliation:
Graduate School, Beijing University of Chinese Medicine, Beijing, China Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Xinmin Liu*
Affiliation:
Department of Gynecology, Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, China
Baoqin Liu*
Affiliation:
TCM Gynecology, China-Japan Friendship Hospital, Beijing, China
*
Corresponding authors: Xinmin Liu; Email: 1351906324@qq.com and Baoqin Liu; Email: baoqinliu529@126.com
Corresponding authors: Xinmin Liu; Email: 1351906324@qq.com and Baoqin Liu; Email: baoqinliu529@126.com
Get access

Abstract

Dysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10−3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.

Type
Article
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of International Society for Twin Studies

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

#

These authors share first authorship.

References

Ahn, S. H., Singh, V., & Tayade, C. (2017). Biomarkers in endometriosis: Challenges and opportunities. Fertility and Sterility, 107, 523532. https://doi.org/10.1016/j.fertnstert.2017.01.009 CrossRefGoogle ScholarPubMed
Amlerova, J., Šroubek, J., Angelucci, F., & Hort, J. (2021). Evidences for a role of gut microbiota in pathogenesis and management of epilepsy. International Journal of Molecular Sciences, 22, 5576. https://doi.org/10.3390/ijms22115576 CrossRefGoogle ScholarPubMed
Arendt-Nielsen, L., Morlion, B., Perrot, S., Dahan, A., Dickenson, A., Kress, H. G., Wells, C., Bouhassira, D., & Drewes, A. M. (2018). Assessment and manifestation of central sensitisation across different chronic pain conditions. European Journal of Pain, 22, 216241. https://doi.org/10.1002/ejp.1140 CrossRefGoogle ScholarPubMed
As-Sanie, S., Kim, J., Schmidt-Wilcke, T., Sundgren, P. C., Clauw, D. J., Napadow, V., & Harris, R. E. (2016). Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. The Journal of Pain, 17, 113. https://doi.org/10.1016/j.jpain.2015.09.008 CrossRefGoogle ScholarPubMed
Bailey, M. T., & Coe, C. L. (2002). Endometriosis is associated with an altered profile of intestinal microflora in female rhesus monkeys. Human Reproduction, 17, 17041708. https://doi.org/10.1093/humrep/17.7.1704 CrossRefGoogle ScholarPubMed
Bowden, J., Davey Smith, G., & Burgess, S. (2015). Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. International Journal of Epidemiology, 44, 512525. https://doi.org/10.1093/ije/dyv080 CrossRefGoogle ScholarPubMed
Bowden, J., Spiller, W., Del Greco, M, F., Sheehan, N., Thompson, J., Minelli, C., & Davey Smith, G. (2018). Improving the visualization, interpretation and analysis of two-sample summary data Mendelian randomization via the radial plot and radial regression. International Journal of Epidemiology, 47, 12641278. https://doi.org/10.1093/ije/dyy101 CrossRefGoogle ScholarPubMed
Burgess, S., Butterworth, A., & Thompson, S. G. (2013). Mendelian randomization analysis with multiple genetic variants using summarized data. Genetic Epidemiology, 37, 658665. https://doi.org/10.1002/gepi.21758 CrossRefGoogle ScholarPubMed
Burgess, S., Thompson, S. G., & CRP CHD Genetics Collaboration. (2011). Avoiding bias from weak instruments in Mendelian randomization studies. International Journal of Epidemiology, 40, 755764. https://doi.org/10.1093/ije/dyr036 CrossRefGoogle ScholarPubMed
Casillas-Espinosa, P. M., Powell, K. L., & O’Brien, T. J. (2012). Regulators of synaptic transmission: Roles in the pathogenesis and treatment of epilepsy. Epilepsia, 53, 4158. https://doi.org/10.1111/epi.12034 CrossRefGoogle ScholarPubMed
Chen, T.-S., Lai, M.-C., Huang, H.-Y. I., Wu, S.-N., & Huang, C.-W. (2022). Immunity, ion channels and epilepsy. International Journal of Molecular Sciences, 23, 6446. https://doi.org/10.3390/ijms23126446 CrossRefGoogle ScholarPubMed
Cui, Z., & Tian, Y. (2021). Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: A Mendelian randomization study. Journal of Translational Medicine, 19, 300. https://doi.org/10.1186/s12967-021-02973-5 CrossRefGoogle ScholarPubMed
Dahlin, M., & Prast-Nielsen, S. (2019). The gut microbiome and epilepsy. EBioMedicine, 44, 741746. https://doi.org/10.1016/j.ebiom.2019.05.024 CrossRefGoogle ScholarPubMed
Davey Smith, G., & Hemani, G. (2014). Mendelian randomization: Genetic anchors for causal inference in epidemiological studies. Human Molecular Genetics, 23, 8998. https://doi.org/10.1093/hmg/ddu328 CrossRefGoogle ScholarPubMed
García-Peñarrubia, P., Ruiz-Alcaraz, A. J., Martínez-Esparza, M., Marín, P., & Machado-Linde, F. (2020). Hypothetical roadmap towards endometriosis: Prenatal endocrine-disrupting chemical pollutant exposure, anogenital distance, gut-genital microbiota and subclinical infections. Human Reproduction Update, 26, 214246. https://doi.org/10.1093/humupd/dmz044 CrossRefGoogle ScholarPubMed
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. (2016). Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet, 388, 15451602. https://doi.org/10.1016/S0140-6736(16)31678-6 CrossRefGoogle Scholar
Greco, M, F. D., Minelli, C., Sheehan, N. A., & Thompson, J. R. (2015). Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Statistics in Medicine, 34, 29262940. https://doi.org/10.1002/sim.6522 CrossRefGoogle Scholar
GWAS Catalog. (n.d.). Trait: dysmenorrhea. https://www.ebi.ac.uk/gwas/efotraits/HP_0100607 Google Scholar
Iacovides, S., Avidon, I., & Baker, F. C. (2015). What we know about primary dysmenorrhea today: A critical review. Human Reproduction Update, 21, 762778. https://doi.org/10.1093/humupd/dmv039 CrossRefGoogle ScholarPubMed
Ingudomnukul, E., Baron-Cohen, S., Wheelwright, S., & Knickmeyer, R. (2007). Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Hormones and Behavior, 51, 597604. https://doi.org/10.1016/j.yhbeh.2007.02.001 CrossRefGoogle ScholarPubMed
Jiang, T., Gill, D., Butterworth, A. S., & Burgess, S. (2023). An empirical investigation into the impact of winner’s curse on estimates from Mendelian randomization. International Journal of Epidemiology, 52, 12091219. https://doi.org/10.1093/ije/dyac233 CrossRefGoogle ScholarPubMed
Josimovich, J. B. (2013). Gynecologic endocrinology. Springer Science & Business Media.Google Scholar
Kamat, M. A., Blackshaw, J. A., Young, R., Surendran, P., Burgess, S., Danesh, J., Butterworth, A. S., & Staley, J. R. (2019). PhenoScanner V2: An expanded tool for searching human genotype-phenotype associations. Bioinformatics, 35, 48514853. https://doi.org/10.1093/bioinformatics/btz469 CrossRefGoogle ScholarPubMed
Kiyama, R. (2020). Nutritional implications of ginger: Chemistry, biological activities and signaling pathways. The Journal of Nutritional Biochemistry, 86, 108486. https://doi.org/10.1016/j.jnutbio.2020.108486 CrossRefGoogle ScholarPubMed
Kwok, M. K., & Schooling, C. M. (2021). Herpes simplex virus and Alzheimer’s disease: A Mendelian randomization study. Neurobiology of Aging, 99, 101.e11101.e13. https://doi.org/10.1016/j.neurobiolaging.2020.09.025 CrossRefGoogle ScholarPubMed
Laschke, M. W., & Menger, M. D. (2016). The gut microbiota: A puppet master in the pathogenesis of endometriosis? American Journal of Obstetrics and Gynecology, 215, 68.e1–4. https://doi.org/10.1016/j.ajog.2016.02.036 CrossRefGoogle ScholarPubMed
Liu, N., Li, Y., Hong, Y., Huo, J., Chang, T., Wang, H., Huang, Y., Li, W., & Zhang, Y. (2023). Altered brain activities in mesocorticolimbic pathway in primary dysmenorrhea patients of long-term menstrual pain. Frontiers in Neuroscience, 17, 1098573. https://doi.org/10.3389/fnins.2023.1098573 CrossRefGoogle ScholarPubMed
McKenna, K. A., & Fogleman, C. D. (2021). Dysmenorrhea. American Family Physician, 104, 164170.Google ScholarPubMed
Octaviana, F., Sumapraja, K., Wiratman, W., Indrawati, L. A., & Budikayanti, A. (2022). Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital. Frontiers in Neurology, 13, 964761. https://doi.org/10.3389/fneur.2022.964761 CrossRefGoogle ScholarPubMed
Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018). The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell, 173, 17281741.e13. https://doi.org/10.1016/j.cell.2018.04.027 CrossRefGoogle ScholarPubMed
Olusanya, B. O., Wright, S. M., Nair, M. K. C., Boo, N.-Y., Halpern, R., Kuper, H., Abubakar, A. A., Almasri, N. A., Arabloo, J., Arora, N. K., Backhaus, S., Berman, B. D., Breinbauer, C., Carr, G., de Vries, P. J., Del Castillo-Hegyi, C., Eftekhari, A., Gladstone, M. J., Hoekstra, R. A., … Global Research on Developmental Disabilities Collaborators (GRDDC). (2020). Global burden of childhood epilepsy, intellectual disability, and sensory impairments. Pediatrics, 146, e20192623. –https://doi.org/10.1542/peds.2019–2623 CrossRefGoogle ScholarPubMed
Pohl, A., Cassidy, S., Auyeung, B., & Baron-Cohen, S. (2014). Uncovering steroidopathy in women with autism: A latent class analysis. Molecular Autism, 5, 27. https://doi.org/10.1186/2040-2392-5-27 CrossRefGoogle ScholarPubMed
Rogers, J. (1964). Menstrual disorders. The New England Journal of Medicine, 270, 356359. https://doi.org/10.1056/NEJM196402132700708 CrossRefGoogle ScholarPubMed
Rosoff, D. B., Clarke, T.-K., Adams, M. J., McIntosh, A. M., Davey Smith, G., Jung, J., & Lohoff, F. W. (2021). Educational attainment impacts drinking behaviors and risk for alcohol dependence: Results from a two-sample Mendelian randomization study with ∼780,000 participants. Molecular Psychiatry, 26, 11191132. https://doi.org/10.1038/s41380-019-0535-9 CrossRefGoogle Scholar
Sandkühler, J. (2009). Models and mechanisms of hyperalgesia and allodynia. Physiological Reviews, 89, 707758. https://doi.org/10.1152/physrev.00025.2008 CrossRefGoogle ScholarPubMed
Sanna, S., van Zuydam, N. R., Mahajan, A., Kurilshikov, A., Vich Vila, A., Võsa, U., Mujagic, Z., Masclee, A. A. M., Jonkers, D. M. A. E., Oosting, M., Joosten, L. A. B., Netea, M. G., Franke, L., Zhernakova, A., Fu, J., Wijmenga, C., & McCarthy, M. I. (2019). Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature Genetics, 51, 600605. https://doi.org/10.1038/s41588-019-0350-x CrossRefGoogle ScholarPubMed
Scheffer, I. E., Berkovic, S., Capovilla, G., Connolly, M. B., French, J., Guilhoto, L., Hirsch, E., Jain, S., Mathern, G. W., Moshé, S. L., Nordli, D. R., Perucca, E., Tomson, T., Wiebe, S., Zhang, Y.-H., & Zuberi, S. M. (2017). ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 58, 512521. https://doi.org/10.1111/epi.13709 CrossRefGoogle ScholarPubMed
Seminowicz, D. A., Laferriere, A. L., Millecamps, M., Yu, J. S. C., Coderre, T. J., & Bushnell, M. C. (2009). MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. NeuroImage, 47, 10071014. https://doi.org/10.1016/j.neuroimage.2009.05.068 CrossRefGoogle Scholar
Serret-Montoya, J., Villasís-Keever, M. A., Ríos-Zúñiga, S., Sánchez-Vaca, G., Zurita-Cruz, J. N., & Hernández-Cabezza, A. (2014). Menstrual pattern characteristics in female adolescents with epilepsy. Revista Medica Del Instituto Mexicano Del Seguro Social, 52, 114119.Google ScholarPubMed
Shim, H., Chasman, D. I., Smith, J. D., Mora, S., Ridker, P. M., Nickerson, D. A., Krauss, R. M., & Stephens, M. (2015). A multivariate genome-wide association analysis of 10 LDL subfractions, and their response to statin treatment, in 1868 Caucasians. PloS One, 10, e0120758. https://doi.org/10.1371/journal.pone.0120758 CrossRefGoogle ScholarPubMed
Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021). The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacological Research, 172, 105840. https://doi.org/10.1016/j.phrs.2021.105840 CrossRefGoogle ScholarPubMed
Sorboni, S. G., Moghaddam, H. S., Jafarzadeh-Esfehani, R., & Soleimanpour, S. (2022). A comprehensive review on the role of the gut microbiome in human neurological disorders. Clinical Microbiology Reviews, 35, e0033820. https://doi.org/10.1128/CMR.00338-20 CrossRefGoogle ScholarPubMed
Verbanck, M., Chen, C.-Y., Neale, B., & Do, R. (2018). Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nature Genetics, 50, 693698. https://doi.org/10.1038/s41588-018-0099-7 CrossRefGoogle ScholarPubMed
Vercellini, P., Viganò, P., Somigliana, E., & Fedele, L. (2014). Endometriosis: Pathogenesis and treatment. Nature Reviews. Endocrinology, 10, 261275. https://doi.org/10.1038/nrendo.2013.255 CrossRefGoogle ScholarPubMed
Vezzani, A., Fujinami, R. S., White, H. S., Preux, P.-M., Blümcke, I., Sander, J. W., & Löscher, W. (2016). Infections, inflammation and epilepsy. Acta Neuropathologica, 131, 211234. https://doi.org/10.1007/s00401-015-1481-5 CrossRefGoogle ScholarPubMed
Wang, H.-X., & Wang, Y.-P. (2016). Gut microbiota-brain axis. Chinese Medical Journal, 129, 23732380. https://doi.org/10.4103/0366-6999.190667 CrossRefGoogle ScholarPubMed
Wang, S., Yao, B., Zhang, H., Xia, L., Yu, S., Peng, X., Xiang, D., & Liu, Z. (2023). Comorbidity of epilepsy and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Journal of Neurology, 270, 42014213. https://doi.org/10.1007/s00415-023-11794-z CrossRefGoogle ScholarPubMed
Winawer, M. R., Connors, R., & Investigators, EPGP. (2013). Evidence for a shared genetic susceptibility to migraine and epilepsy. Epilepsia, 54, 288295. https://doi.org/10.1111/epi.12072 CrossRefGoogle ScholarPubMed
Woolf, C. J. (2011). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 152, S2S15. https://doi.org/10.1016/j.pain.2010.09.030 CrossRefGoogle ScholarPubMed
Ye, X., Liu, B., Bai, Y., Cao, Y., Lin, S., Lyu, L., Meng, H., Dai, Y., Ye, D., Pan, W., Wang, Z., Mao, Y., & Chen, Q. (2023). Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: Insights from a two-sample Mendelian randomization study. Journal of Translational Medicine, 21, 674. https://doi.org/10.1186/s12967-023-04559-9 CrossRefGoogle ScholarPubMed
Yue, Q., Cai, M., Xiao, B., Zhan, Q., & Zeng, C. (2022). The Microbiota-Gut-Brain Axis and Epilepsy. Cellular and Molecular Neurobiology, 42, 439453. https://doi.org/10.1007/s10571-021-01130-2 CrossRefGoogle ScholarPubMed
Zarcone, D., & Corbetta, S. (2017). Shared mechanisms of epilepsy, migraine and affective disorders. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 38, 7376. https://doi.org/10.1007/s10072-017-2902-0 CrossRefGoogle ScholarPubMed
Supplementary material: File

Ren et al. supplementary material

Ren et al. supplementary material

Download Ren et al. supplementary material(File)
File 12.7 KB