Introduction:
Migraine is a prevalent and debilitating neurovascular disorder, affecting approximately 14% of the global population. Growing evidence suggest a potential relationship between the gut microbiome and migraine, mediated by the gut-brain axis. This research aims to investigate the genetic relationship between migraine and the human gut microbiome through cross-trait statistical genetic analyses.
Methodology:
We utilized summary statistics from the largest available genome-wide association studies (GWASs) for migraine and hundreds of microbial traits. We used LDSC and HDL to estimate genome-wide SNP-based heritability and cross-trait genetic correlations between migraine and each microbiome trait. Local heritability and genetic correlation were assessed using LAVA and HDL-L. Additionally, we applied GWAS-PW to detect pleiotropic regions and MiXeR to estimate the number of shared causal variants between migraine and the microbiome traits.
Results:
Although several microbiome traits produced evidence for SNP-based heritability, none showed a significant genome-wide genetic correlation with migraine. In contrast, local analyses successfully identified multiple loci with significant regional genetic correlations between specific microbial traits and migraine. We further pinpointed several pleiotropic regions with a posterior probability of shared association of more than 0.5 using GWAS-PW. MiXeR analysis also revealed a significant number of shared causal variants for migraine and various gut microbiome traits.
Discussion:
Our findings suggest that gut microbiome composition may play a role in migraine pathophysiology, with certain microbial taxa showing potential as biomarkers for migraine susceptibility. While we did not find significant genome-wide genetic correlations across the traits, we identified several loci showing significant genetic correlations between the traits, highlighting the importance of local analyses. The analyses conducted so far identify shared genetic architecture but do not confirm causal relationships. Next, we will perform bidirectional Mendelian randomization to test for a causal relationship between migraine and the gut microbiome.