Epidemiological studies have reported a comorbid relationship between migraine and thyroid dysfunction.
We investigated the genetic relationship between migraine and thyroid function traits using genome-wide association study (GWAS) data.
We found a significant genetic correlation () with migraine for hypothyroidism ( = 0.0608), secondary hypothyroidism ( = 0.195), free thyroxine (fT4) ( = 0.0772), and hyperthyroidism ( = -0.1046), but not thyroid stimulating hormone (TSH). Pairwise GWAS analysis revealed two shared loci with TSH and 11 shared loci with fT4. Cross-trait GWAS meta-analysis of migraine identified novel genome-wide significant loci: 17 with hypothyroidism, one with hyperthyroidism, five with secondary hypothyroidism, eight with TSH, and 15 with fT4. Of the genes at these loci, six (, , , , , ; migraine + hypothyroidism), three (, , ; migraine + TSH), and three (, , ; migraine + fT4) were significant in our gene-based analysis ( < 2.04 × 10). In addition, causal analyses suggested a negative causal relationship between migraine and hyperthyroidism ( = 8.90 × 10) and a positive causal relationship between migraine and secondary hypothyroidism ( = 1.30 × 10).
These findings provide strong evidence for genetic correlation and suggest complex causal relationships between migraine and thyroid traits.