Migraine and Ischemic Stroke: A Mendelian Randomization Study
Tóm tắt
Previous epidemiological studies have found an increased risk for ischemic stroke in patients with migraine; however, the evidence for a causal relationship between migraine and ischemic stroke is scarce. This study aims to explore the potential causal relationship between migraine and ischemic stroke and its subtypes [including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES)]. We used data on genetic variants associated with migraine identified from a genome-wide association study (GWAS) meta-analysis among 889,018 European ancestries. Summary data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium including up to 438,847 participants. We performed two-sample Mendelian randomization (MR) analyses using the inverse-variance-weighted method as the primary approach. The MR-Egger, weighted median, simple median, simple mode, and weighted mode methods were also conducted as sensitivity analyses to determine the robustness of our results. We failed to detect statistically significant associations between migraine and ischemic stroke (OR, 0.935; 95% CI 0.851–1.027; P = 0.159) and its subtypes (LAS: OR, 0.818; 95% CI 0.692–0.967; P = 0.018) (SVS: OR, 0.935; 95% CI 0.781–1.119; P = 0.460) (CES: OR, 1.015; 95% CI 0.867–1.189; P = 0.850). The results were consistent with the sensitivity analyses. By conducting a series of causal inference approaches, this study supports no causal effect of migraine on ischemic stroke and its subtypes.
Tài liệu tham khảo
Vos T, Abajobir AA, Abate KH, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England). 2017;390(10100):1211–59.
Mahmoud AN, Mentias A, Elgendy AY, et al. Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1,152,407 subjects. BMJ Open. 2018;8(3):e020498.
Gryglas A, Smigiel R. Migraine and stroke: what’s the link? What to do? Curr Neurol Neurosci Rep. 2017;17(3):22.
Lantz M, Sieurin J, Sjölander A, Waldenlind E, Sjöstrand C, Wirdefeldt K. Migraine and risk of stroke: a national population-based twin study. Brain. 2017;140(10):2653–62.
Tietjen GE. Migraine as a systemic disorder. Neurology. 2007;68(19):1555–6.
Eikermann-Haerter K. Spreading depolarization may link migraine and stroke. Headache. 2014;54(7):1146–57.
Bochud M (2008) On the use of Mendelian randomization to infer causality in observational epidemiology. Eur Heart J. 2008; 29:2456–57.
Choquet H, Yin J, Jacobson AS, et al. New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis. Commun Biol. 2021;4(1):864.
Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018;50(4):524–37.
Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey SG. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133–63.
Turk WE, Uiterwijk A, Pasmans R, Meys V, Ayata C, Koehler PJ. Aspirin prophylaxis for migraine with aura: an observational case series. Eur Neurol. 2017;78: 287–9.
Maggioni F, Bruno M, Mainardi F, Lisotto C, Zanchin G. Migraine responsive to warfarin: an update on anticoagulant possible role in migraine prophylaxis. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2012;33(6):1447–9.
Emdin CA, Khera AV, Kathiresan S. Mendelian Randomization. JAMA. 2017;318(19):1925–6.
Gormley P, Anttila V, Winsvold BS, et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet. 2016;48(8):856–66.
Auton A, Brooks LD, Durbin RM, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.
Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64.
Nikolakopoulou A, Mavridis D, Salanti G. How to interpret meta-analysis models: fixed effect and random effects meta-analyses. Evid Based Ment Health. 2014;17(2):64.
Bowden J, Del Greco MF, 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):1783–802.
Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.
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(5):693–8.
Kurth T, Chabriat H, Bousser M-G. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11(1):92–100.
Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63.
Malik R, Freilinger T, Winsvold BS, et al. Shared genetic basis for migraine and ischemic stroke: a genome-wide analysis of common variants. Neurology. 2015;84(21):2132–45.
Siewert KM, Klarin D, Damrauer SM, et al. Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache. Int J Epidemiol. 2020;49(3):1022–31.
Vongvaivanich K, Lertakyamanee P, Silberstein SD, Dodick DW. Late-life migraine accompaniments: a narrative review. Cephalalgia. 2015;35(10):894–911.
Burgess S, Butterworth AS, Thompson JR, et al. Guidelines for performing Mendelian randomization investigations. Wellcome open Res. 2019;4:186.