TY - JOUR
T1 - Shared genetics and causal relationships between migraine and thyroid function traits
AU - The International Headache Genetics Consortium (IHGC)
AU - Tasnim, Sana
AU - Wilson, Scott G.
AU - Walsh, John P.
AU - Nyholt, Dale R.
N1 - Funding Information:
We would like to thank the research participants and employees of 23andMe, Inc. for making this work possible. The full GWAS summary statistics for the 23andMe discovery data set will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. Please visit https://research.23andme.com/collaborate/#dataset-access/ for more information and to apply to access the data. In addition, we acknowledge the contributions of the PANUK Biobank, the International Headache Genetics Consortium (IHGC), and the ThyroidOmics consortium (Teumer et al. 2018) for sharing their data. The first author would like to thank the Queensland University of Technology (QUT) and the Australian Government's Research Training Program (RTP) for providing a scholarship.
Publisher Copyright:
© The Author(s) 2023.
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 -