Shared genetics and causal relationships between migraine and thyroid function traits

Sana Tasnim, Scott G. Wilson, John P. Walsh, Dale R. Nyholt, (IHGC) International Headache Genetics Consortium

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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 (rg) with migraine for hypothyroidism (rg = 0.0608), secondary hypothyroidism (rg = 0.195), free thyroxine (fT4) (rg = 0.0772), and hyperthyroidism (rg = –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 (pFisher’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.

Original languageEnglish
Number of pages15
JournalCephalalgia
Volume43
Issue number2
DOIs
Publication statusPublished - 5 Feb 2023

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