Introduction: To investigate the association of genetically predicted migraine with the risk of primary open-angle glaucoma (POAG). Methods: To estimate the shared genetic basis of migraine and POAG, we conducted genome-wide genetic correlation analyses using cross-trait linkage disequilibrium score regression. To assess potential causal effects of migraine on POAG risk, we conducted two-sample Mendelian randomization (MR) analyses using data from European ancestry individuals. Genetic instruments (N = 54 genetic variants with minor allele frequency (MAF) ≥ 0.01) were derived from our previous genome-wide association study (GWAS) of migraine conducted in the UK Biobank (16,709 migraine cases and 438,178 controls). For POAG, we used GWAS summary statistics from our previous GWAS conducted in the GERA cohort (3836 POAG cases and 48,065 controls) or using data from the International Glaucoma Genetics Consortium (15,229 POAG cases and 177,473 controls). The inverse-variance weighted (IVW) method was our primary source of MR estimates and common sensitivity analyses were conducted. Results: We found that migraine was not genetically associated with POAG ( r _g = 0.05; SE = 0.11; P  = 0.69). Further, we did not detect any evidence of association between genetically predicted migraine with POAG. Conclusion: Our results provide evidence that genetic risk for migraine may not be a strong causal risk factor for POAG.

Migraine is characterized by severe pain and somatic symptoms like allodynia and photophobia, driven by neuroinflammation that sensitizes the trigeminal vascular system (TVS). This study investigated how neuroinflammation induced by systemic lipopolysaccharide (LPS) affects migraine-related nociceptive signaling. Using a chronic migraine model in rats with nitroglycerin (NTG), we compared prenatal and acute postnatal LPS administration. Rats with prenatal LPS exhibited lower mechanical thresholds and enhanced allodynia and photophobia after NTG. Acute LPS also increased allodynia, but not photophobia. Both LPS groups showed increased mast cell degranulation in the dura mater. Plasma CGRP after NTG administration was elevated in the acute LPS group. Electrophysiology revealed enhanced trigeminal afferent responses to serotonin in both acutely and prenatally LPS-treated rats. Calcium imaging demonstrated increased neuronal responses to serotonin and capsaicin, suggesting an upregulation of serotonin and TRPV1 receptors. Our findings show that LPS-induced neuroinflammation, whether prenatal or acute, promotes sensitization of peripheral and central nociceptive pathways, involving serotoninergic mechanisms.

Background: Migraine is one of the most common diseases that significantly impairs the quality of life. This condition has a pronounced genetic component. Genes responsible for the development of monogenic forms of hemiplegic migraine have already been identified, and the search for genetic associations with common migraine and its subtypes continues. Objective: The aim of this study was to search for new potential genetic markers of migraine by analyzing available open genetic databases. Methods: The analysis included databases such as ClinVar, GWAS Catalog, UK Biobank and FinnGen. In all databases, the keyword "migraine" was used to search for migraineassociated variants. Genetic variants with clinical annotations "pathogenic" and "likely pathogenic" were selected from the variants in the ClinVar database. From other databases, variants with an association significance level of p ≤ 5×10-8 were chosen. Results: A total of 112 genetic variants associated with migraine were identified. After excluding polymorphisms known from previous migraine studies, it was found that 45 genetic variants were identified for the first time. Conclusion: These variants belong to various functional groups, including ion channels, enzymes, receptors, and regulatory proteins, confirming the current understanding of the polygenic nature of migraine. Identifying new genetic associations with migraine can contribute to a better understanding of its pathogenesis and open new possibilities for diagnosis and the development of more effective treatment strategies for this condition.