A genetic analysis uncovered significant shared genetic connections between migraine and various gastrointestinal disorders. 

In the study, published in Neurology Genetics, researchers utilized data from genome-wide association studies (GWAS) to compare migraine with conditions such as irritable bowel syndrome (IBS), peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), functional dyspepsia (FD), diverticular disease (DD), and inflammatory bowel disease (IBD).

The strongest genetic correlation was identified between migraine and IBS (ρg = 0.37, P = 1.0 × 10⁻²¹), followed by GERD (ρg = 0.34, P = 2.2 × 10⁻³¹) and FD (ρg = 0.34, P = 2.2 × 10⁻³¹). Conversely, immune-mediated conditions such as IBD showed no significant genetic correlations. The genetic overlap concentrated in regions associated with central nervous system (CNS) expression, suggesting neurological underpinnings.

Mendelian randomization revealed a causal association of certain gastrointestinal (GI) disorders with migraine risk. DD exhibited the strongest association (ΩR = 1.90, P = 2.2 × 10⁻⁴), while GERD and PUD also showed significant connections. No evidence supported a causal pathway from migraine to GI disorders. Notably, genetic variation at the CGRP locus (CALCA/CALCB genes) demonstrated inverse correlations between migraine and some GI conditions like GERD, potentially informing therapeutic strategies.

The study predominantly included patients of European ancestry, limiting generalizability. The findings underscored the role of neurologic mechanisms in the comorbidity of migraine and GI disorders while suggesting avenues for targeted treatment, particularly through the CGRP pathway.

Funding for the research was provided by grants from NINDS/NIH, the American Heart Association, and NIDDK/NIH. The authors disclosed no relevant financial conflicts of interest.