Statistical and Genomic Epidemiology Laboratory, School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Australia.
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
Cephalalgia. 2023 Feb;43(2):3331024221139253. doi: 10.1177/03331024221139253.
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.
流行病学研究报告偏头痛与甲状腺功能障碍之间存在共病关系。
我们使用全基因组关联研究（GWAS）数据研究偏头痛与甲状腺功能特征之间的遗传关系。
我们发现甲状腺功能减退症（ = 0.0608）、继发性甲状腺功能减退症（ = 0.195）、游离甲状腺素（fT4）（ = 0.0772）和甲状腺功能亢进症（ = -0.1046）与偏头痛存在显著的遗传相关性，但甲状腺刺激激素（TSH）除外。成对 GWAS 分析显示 TSH 与两个共享位点，fT4 与 11 个共享位点。偏头痛的跨特征 GWAS 荟萃分析确定了新的全基因组显著位点：17 个与甲状腺功能减退症相关，1 个与甲状腺功能亢进症相关，5 个与继发性甲状腺功能减退症相关，8 个与 TSH 相关，15 个与 fT4 相关。在这些位点的基因中，有六个（,,,,, ；偏头痛 + 甲状腺功能减退症）、三个（,, ；偏头痛 + TSH）和三个（,, ；偏头痛 + fT4）在我们的基于基因的分析中具有显著意义（ < 2.04 × 10）。此外，因果分析表明偏头痛与甲状腺功能亢进症之间存在负向因果关系（ = 8.90 × 10），偏头痛与继发性甲状腺功能减退症之间存在正向因果关系（ = 1.30 × 10）。
这些发现为偏头痛与甲状腺特征之间的遗传相关性提供了强有力的证据，并表明两者之间存在复杂的因果关系。
