Genetic correlations between migraine and carpal tunnel syndrome

Abstract

Background: Surgical deactivation of extracranial nerve trigger sites is now well-established as an effective treatment for migraine headache. Parallels have been drawn to median nerve decompression for carpal tunnel syndrome (CTS), and two previous studies have demonstrated an association between migraine and CTS. We sought to: (1) substantiate these findings in a considerably larger UK cohort, and; (2) investigate potential genetic associations between the two disorders. Methods: Nested case-control studies were conducted in the UK Biobank cohort of 401,656 individuals. Odds ratios were calculated for the association between migraine and CTS in the overall cohort and sex-stratified subsets. Genetic correlation between migraine and CTS was interrogated by linkage disequilibrium score regression (LDSC), leveraging data from published genome-wide association studies. Regions of genetic overlap were identified by Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC). Results: Migraine and CTS show a significant epidemiological association within UK Biobank (OR=1.14, 95% CI: 1.04–1.25, p=0.0058), which is specific to females (OR=1.15; 95% CI: 1.04–1.28, p=0.0057) and not males (OR=1.07; 95% CI: 0.82–1.40, p=0.61). Genetic analysis demonstrated a significant positive genetic correlation between the two disorders (rg=0.13, p=0.0039), and implicated the TRIM32 locus on chromosome 9 as a region of genetic overlap. Conclusions: This study replicates past reports of an epidemiological association between CTS and migraine, albeit in females only. This association is underpinned by a genetic correlation, with shared genetic susceptibility at the TRIM32 locus. Our data adds credibility to the notion that an element of entrapment neuropathy underlies migraine pathophysiology.