全基因组关联研究揭示了大型基于社区的亚洲人群中自我报告头痛的易感基因位点。

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

机构信息

Department of Internal Medicine, 156932Yonghe Cardinal Tien Hospital, Yonghe Cardinal Tien Hospital, Taipei, Taiwan.

Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

Cephalalgia. 2022 Mar;42(3):229-238. doi: 10.1177/03331024211037269. Epub 2021 Aug 18.

DOI:10.1177/03331024211037269

PMID:34404248

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 and rs13312779 in , 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 ( = 8.53 × 10 and = 1.07 × 10, respectively). Gene enrichment analysis for genes with GWAS suggestive significance ( < 10) demonstrated that the expression of these genes was significantly enriched in the artery ( = 8.18 × 10) and adipose tissue ( = 8.95 × 10).

CONCLUSION

Our results suggest that vascular dysfunction might play important roles in the pathogenesis of self-reported headache in Asian populations.

摘要

背景

在亚洲人群中，尚未确定普通人群头痛的遗传基础。我们在一个大型基于社区的亚洲人群中研究了易患头痛的易感遗传变异。

方法

我们对从基于社区的队列中招募的参与者进行了全基因组关联研究，以鉴定与台湾人自述头痛相关的遗传变异。所有参与者都接受了关于自述头痛的结构化问卷调查。共纳入 2084 名“自述头痛”患者和 11822 名年龄和性别匹配的对照者。使用基因型-组织表达版本 6 数据库进行基因富集分析，以探讨鉴定出的变异体的潜在功能。

结果

我们确定了两个新的位点，即位于中的 rs10493859 和位于中的 rs13312779，它们与血管功能和偏头痛密切相关，经年龄、性别和前 10 个主要成分校正后，与自述头痛显著相关（ = 8.53 × 10 和 = 1.07 × 10 ，分别）。对具有 GWAS 提示意义的基因（ < 10）进行基因富集分析表明，这些基因的表达在动脉（ = 8.18 × 10）和脂肪组织（ = 8.95 × 10）中显著富集。