Department of Forensic Medicine, School of Medicine and Forensics, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, 710061, Shaanxi, China.
Department of Neurology, Xijing Hospital of Air Force Medical University, Xi'an, Shaanxi, China.
Sci Rep. 2021 Mar 24;11(1):6807. doi: 10.1038/s41598-021-86374-0.
A recent genome-wide meta study suggested that rs67338227 in the FHL5 gene and rs10456100 in the KCNK5 gene are associated with migraine from 27 population-based cohorts excluding Chinese population. Given that migraine without aura (MO) is the most common subtype of migraine, our aim was to systematically investigate the relationship of common variants in FHL5 and KCNK5 genes with the susceptibility to MO and provide clues as to the nature of the mechanisms involved in the etiology of migraine. A total of 3306 subjects including 1042 patients with MO and 2264 controls were recruited for the discovery stage, and 2530 individuals including 842 patients with MO and 1688 controls for the replication stage. Twenty-two tag SNPs (7 from FHL5 and 15 from KCNK5) were selected for genotyping. Genetic associations were analyzed at both single-marker and haplotype levels. Potential functional consequences of the significant SNPs were analyzed using gene expression data obtained from the GTEx database. Two SNPs, rs10456100 (KCNK5, P = 9.01 × 10) and rs7775721 (FHL5, P = 6.86 × 10), were determined to be significantly associated with MO in the discovery sample and were then replicated in another sample. In the combined sample set, the T allele of both SNPs was significantly associated with the increased risk of MO. Significant eQTL signals were identified for both SNP rs10456100 and rs7775721. Our findings suggest that the T allele carriers of SNP rs10456100 and rs7775721 are at increased risk of migraine.
最近的全基因组荟萃分析研究表明，FHL5 基因中的 rs67338227 和 KCNK5 基因中的 rs10456100 与来自 27 个人群队列的偏头痛相关，这些队列排除了中国人群。鉴于无先兆偏头痛 (MO) 是偏头痛最常见的亚型，我们的目的是系统研究 FHL5 和 KCNK5 基因中的常见变异与 MO 易感性的关系，并为偏头痛发病机制中涉及的机制性质提供线索。共有 3306 名受试者，包括 1042 名 MO 患者和 2264 名对照者，用于发现阶段，共有 2530 名个体，包括 842 名 MO 患者和 1688 名对照者，用于复制阶段。选择了 22 个标签 SNP（7 个来自 FHL5，15 个来自 KCNK5）进行基因分型。在单标记和单倍型水平上分析了遗传关联。使用来自 GTEx 数据库的基因表达数据分析了显著 SNP 的潜在功能后果。两个 SNP，rs10456100（KCNK5，P=9.01×10）和 rs7775721（FHL5，P=6.86×10），在发现样本中被确定与 MO 显著相关，然后在另一个样本中得到复制。在合并样本集中，两个 SNP 的 T 等位基因与 MO 风险增加显著相关。rs10456100 和 rs7775721 均存在显著的 eQTL 信号。我们的研究结果表明，SNP rs10456100 和 rs7775721 的 T 等位基因携带者患偏头痛的风险增加。
