Shared genetics and causal relationships between migraine and thyroid function traits.

BACKGROUND: Epidemiological studies have reported a comorbid relationship between migraine and thyroid dysfunction.

METHODS: We investigated the genetic relationship between migraine and thyroid function traits using genome-wide association study (GWAS) data.

RESULTS: We found a significant genetic correlation ( r g ) with migraine for hypothyroidism ( r g  = 0.0608), secondary hypothyroidism ( r g  = 0.195), free thyroxine (fT4) ( r g  = 0.0772), and hyperthyroidism ( r g  = -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 ( RERE , TGFB2 , APLF , SLC9B1 , SGTB , BTBD16 ; migraine + hypothyroidism), three ( GADD45A , PFDN1 , RSPH6A ; migraine + TSH), and three ( SSBP3 , BRD3 , TEF ; migraine + fT4) were significant in our gene-based analysis ( p Fisher's combined P-value  < 2.04 × 10-6 ). In addition, causal analyses suggested a negative causal relationship between migraine and hyperthyroidism ( p  = 8.90 × 10-3 ) and a positive causal relationship between migraine and secondary hypothyroidism ( p  = 1.30 × 10-3 ).

CONCLUSION: These findings provide strong evidence for genetic correlation and suggest complex causal relationships between migraine and thyroid traits.