Common variants in KCNK5 and FHL5 genes contributed to the susceptibility of migraine without aura in Han Chinese population

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 × 10–9) and rs7775721 (FHL5, P = 6.86 × 10–13), 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.