Abstract
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.