Genome-wide association study reveals susceptibility loci for self-reported headache in a large community-based Asian population

Background: The genetic substrate for headache in the general population has not been identified in Asians. We investigated susceptible genetic variants for self-reported headache in a large community-based Asian population. Methods: We conducted a genome-wide association study in participants recruited from a community-based cohort to identify the genetic variants associated with headache in Taiwanese. All participants received a structured questionnaire for self-reported headache. A total of 2084 patients with “self-reported headache” and 11,822 age- and sex-matched controls were enrolled. Gene enrichment analysis using the Genotype-Tissue Expression version 6 database was performed to explore the potential function of the identified variants. Results: We identified two novel loci, rs10493859 in TGFBR3 and rs13312779 in FGF23, that are functionally relevant to vascular function and migraine to be significantly associated with self-reported headache after adjusting age, sex and top 10 principal components (p = 8.53 × 10⁻¹¹ and p = 1.07 × 10⁻⁸, respectively). Gene enrichment analysis for genes with GWAS suggestive significance (p < 10⁻⁶) demonstrated that the expression of these genes was significantly enriched in the artery (p = 8.18 × 10⁻⁴) and adipose tissue (p = 8.95 × 10⁻⁴). Conclusion: Our results suggest that vascular dysfunction might play important roles in the pathogenesis of self-reported headache in Asian populations.