Genome-wide association study reveals susceptibility loci for self-reported headache in a large community-based Asian population. (March 2022)

• Record Type: Journal Article
• Authors: Tsao, Yu-Chien; Wang, Shuu-Jiun; Hsu, Chia-Lin; Wang, Yen-Feng; Fuh, Jong-Ling; Chen, Shih-Pin; Fann, Cathy Shen-Jang
• Is Part Of: Cephalalgia. Volume 42:Number 3(2022)
• Page Start: 229
• Page End: 238
• Publication Date: 2022-03
• Subjects: Headache -- genome-wide association -- TGFBR3 -- FGF23 -- tissue expression; Headache -- Periodicals; 616.8491
• DOI: 10.1177/03331024211037269
• Languages: English
• ISSNs: 0333-1024

Abstract

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.