TY - JOUR
T1 - Shared genetics and causal relationships between migraine and thyroid function traits
AU - Tasnim, Sana
AU - Wilson, Scott G.
AU - Walsh, John P.
AU - Nyholt, Dale R.
AU - International Headache Genetics Consortium , (IHGC)
PY - 2023/2/5
Y1 - 2023/2/5
N2 - 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.
AB - 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.
KW - causal relationship
KW - cross-trait meta-analysis
KW - gene-based analysis
KW - GWAS
KW - Migraine
KW - pairwise-GWAS
KW - thyroid dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85146742165&partnerID=8YFLogxK
U2 - 10.1177/03331024221139253
DO - 10.1177/03331024221139253
M3 - Article
C2 - 36739509
AN - SCOPUS:85146742165
SN - 0333-1024
VL - 43
JO - Cephalalgia
JF - Cephalalgia
IS - 2
ER -