期刊
CEPHALALGIA
卷 42, 期 3, 页码 229-238出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/03331024211037269
关键词
Headache; genome-wide association; TGFBR3; FGF23; tissue expression
资金
- Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program
- Ministry of Science and Technology, Taiwan [MOST-107-2314-B-010-021, 108-2314-B-010-022-MY3, MOST 110-2326-B-A49A-501-MY3, MOST 108-2321-B-010-014-MY2, MOST 108-2321-B-010-001, MOST 108-2314-B-010-023-MY3, MOST 110-2321-B-010 -005, MOST 108-2314-B-001-007, MOST 109-2314-B-001 -006 -MY2]
- Ministry of Health and Welfare, Taiwan [MOHW107-TDU-B-211-123001, MOHW 108-TDU-B-211-133001]
- Taipei Veterans General Hospital, Taiwan [VGH-109-C-090, V109E-005-1, VGH-109-C-139, VGH-109-D52-001-MY3-1]
This study identified two novel loci, rs10493859 in TGFBR3 and rs13312779 in FGF23, associated with self-reported headache in Asian populations. Gene enrichment analysis indicated that these genes were significantly enriched in artery and adipose tissue. These results suggest that vascular dysfunction may play a role in the pathogenesis of self-reported headache in Asians.
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 x 10(-11) and p = 1.07 x 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 x 10(-4)) and adipose tissue (p = 8.95 x 10(-4)). Conclusion Our results suggest that vascular dysfunction might play important roles in the pathogenesis of self-reported headache in Asian populations.
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