Brain Structures As Potential Mediators of the Causal Effect of COVID 19 on Migraine Risk

Overview

Journal Sci Rep

Specialty Science

Date 2024 Nov 13

PMID 39537835

Authors

Hongbei Xu

Wei Chen

Yaxin Ju

Hongqun Chen

Ping Yuan

Fu Ouyang

Affiliations

Soon will be listed here.

Abstract

Migraine is a common neurological disorder observed after coronavirus disease 2019 (COVID 19) infection. However, the intricate relationship between COVID 19 and migraine, particularly the potential mediating role of brain imaging-derived phenotypes (BIPs), remains unclear. This study used linkage disequilibrium score regression (LDSC), a bidirectional two-sample Mendelian randomization (MR) approach, and two-step MR analysis to investigate potential causal links. The robustness of the MR findings was corroborated through generalized summary-data-based Mendelian randomization (GSMR) and MR-Steiger methods. The results of the LDSC analysis revealed that the genetic correlation coefficient between COVID 19 traits and migraine was 0.0277 for infection (P = 0.0051), 0.1690 for hospitalization (P = 0.0016), and 0.1147 for severity (P = 0.0330). The genetic correlation coefficients between COVID 19 infection, hospitalization, severity and migraine and migraine with aura (MA) were 0.2654 (P = 0.0012), 0.2065 (P = 0.0043), and 0.1537 (P = 0.0230), respectively. Two-sample MR analysis revealed a significant causal association of COVID 19 infection (odds ratio [OR] 1.2502, P = 0.0083; OR 1.4956, P = 0.0084), hospitalization (OR 1.0689, P = 0.0138; OR 1.0919, P = 0.0208), and severity (OR 1.0644, P = 0.0072; OR 1.0844, P = 0.0098) with increased risk of migraine and migraine with aura (MA). Cortical thickness (CT), total surface area (TSA), and fractional anisotropy (FA) were identified as BIP intermediaries in the risk trajectory from COVID 19 to migraine. The TSA exhibited a more pronounced mediating effect than did CT. This study revealed that genetically predicted COVID 19 is associated with an increased risk of migraine and MA, and BIPs act as potential mediators of these causal relationships, offering insights into the neurobiological underpinnings of migraine in the context of COVID 19.

References

Madera J, Rodriguez-Rodriguez E, Gonzalez-Quintanilla V, Perez-Pereda S, Pascual J . [Peripheral stimulation of the trigeminal nerve by nasopharyngeal swabbing as a possible trigger of migraine attacks]. Rev Neurol. 2023; 76(7):227-233. PMC: 10478117. DOI: 10.33588/rn.7607.2022271. View

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

Lu Y, Li X, Geng D, Mei N, Wu P, Huang C . Cerebral Micro-Structural Changes in COVID-19 Patients - An MRI-based 3-month Follow-up Study. EClinicalMedicine. 2020; 25:100484. PMC: 7396952. DOI: 10.1016/j.eclinm.2020.100484. View

Duncan L, Shen H, Ballon J, Hardy K, Noordsy D, Levinson D . Genetic Correlation Profile of Schizophrenia Mirrors Epidemiological Results and Suggests Link Between Polygenic and Rare Variant (22q11.2) Cases of Schizophrenia. Schizophr Bull. 2018; 44(6):1350-1361. PMC: 6192473. DOI: 10.1093/schbul/sbx174. View

Planchuelo-Gomez A, Garcia-Azorin D, Guerrero A, Aja-Fernandez S, Rodriguez M, de Luis-Garcia R . White matter changes in chronic and episodic migraine: a diffusion tensor imaging study. J Headache Pain. 2020; 21(1):1. PMC: 6941267. DOI: 10.1186/s10194-019-1071-3. View

Sampaio Rocha-Filho P, Mota Albuquerque P, Carvalho L, Gama M, Magalhaes J . Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study. J Headache Pain. 2022; 23(1):2. PMC: 8721484. DOI: 10.1186/s10194-021-01367-8. View

Cohen J, Chalumeau M, Cohen R, Korevaar D, Khoshnood B, Bossuyt P . Cochran's Q test was useful to assess heterogeneity in likelihood ratios in studies of diagnostic accuracy. J Clin Epidemiol. 2014; 68(3):299-306. DOI: 10.1016/j.jclinepi.2014.09.005. View

Zhou S, Wei T, Liu X, Liu Y, Song W, Que X . Causal effects of COVID-19 on structural changes in specific brain regions: a Mendelian randomization study. BMC Med. 2023; 21(1):261. PMC: 10354891. DOI: 10.1186/s12916-023-02952-1. View

Maleki N, Becerra L, Nutile L, Pendse G, Brawn J, Bigal M . Migraine attacks the Basal Ganglia. Mol Pain. 2011; 7:71. PMC: 3192678. DOI: 10.1186/1744-8069-7-71. View

10.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

11.

Yoon B, Buch K, Lang M, Applewhite B, Li M, Mehan Jr W . Clinical and Neuroimaging Correlation in Patients with COVID-19. AJNR Am J Neuroradiol. 2020; 41(10):1791-1796. PMC: 7661080. DOI: 10.3174/ajnr.A6717. View

12.

Yang G, Schooling C . Genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and health outcomes: a drug-target Mendelian randomization study and a phenome-wide association study. BMC Med. 2023; 21(1):235. PMC: 10318778. DOI: 10.1186/s12916-023-02903-w. View

13.

Eyler L, Chen C, Panizzon M, Fennema-Notestine C, Neale M, Jak A . A comparison of heritability maps of cortical surface area and thickness and the influence of adjustment for whole brain measures: a magnetic resonance imaging twin study. Twin Res Hum Genet. 2012; 15(3):304-14. PMC: 3549553. DOI: 10.1017/thg.2012.3. View

14.

DaSilva A, Granziera C, Snyder J, Hadjikhani N . Thickening in the somatosensory cortex of patients with migraine. Neurology. 2007; 69(21):1990-5. PMC: 3757544. DOI: 10.1212/01.wnl.0000291618.32247.2d. View

15.

Verhagen I, van Casteren D, de Vries Lentsch S, Terwindt G . Effect of lockdown during COVID-19 on migraine: A longitudinal cohort study. Cephalalgia. 2021; 41(7):865-870. PMC: 8166402. DOI: 10.1177/0333102420981739. View

16.

Burstein R, Jakubowski M, Garcia-Nicas E, Kainz V, Bajwa Z, Hargreaves R . Thalamic sensitization transforms localized pain into widespread allodynia. Ann Neurol. 2010; 68(1):81-91. PMC: 2930514. DOI: 10.1002/ana.21994. View

17.

Bulik-Sullivan B, Finucane H, Anttila V, Gusev A, Day F, Loh P . An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015; 47(11):1236-41. PMC: 4797329. DOI: 10.1038/ng.3406. View

18.

Lutz S, Voorhies K, Wu A, Hokanson J, Vansteelandt S, Lange C . The influence of unmeasured confounding on the MR Steiger approach. Genet Epidemiol. 2022; 46(2):139-141. PMC: 8915443. DOI: 10.1002/gepi.22442. View

19.

Hoogman M, Muetzel R, Guimaraes J, Shumskaya E, Mennes M, Zwiers M . Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples. Am J Psychiatry. 2019; 176(7):531-542. PMC: 6879185. DOI: 10.1176/appi.ajp.2019.18091033. View

20.

Moulton E, Burstein R, Tully S, Hargreaves R, Becerra L, Borsook D . Interictal dysfunction of a brainstem descending modulatory center in migraine patients. PLoS One. 2008; 3(11):e3799. PMC: 2582961. DOI: 10.1371/journal.pone.0003799. View