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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.

A constant ratio of ferritin heavy chain homolog (HCH) and light chain homolog (LCH) subunits seems to be required to compose the ferritin heteropolymer protein in insects. However, the mechanism by which insect LCH genes regulate protein levels remains unclear. We report that alternative promoters and alternative splicing contribute to maintaining a constant ratio of the two subunits, BdFer1HCH and BdFer2LCH (ferritin 1 HCH and ferritin 2 LCH), in Bactrocera dorsalis, a notorious quarantine pest. The genes BdFer1HCH and BdFer2LCH were identified with a series of potential transcription factor binding sites and were shown to be clustered within the genome in a "head to head" fashion. Thus, we unearthed a potential post-transcriptional mechanism to regulate the levels of LCH subunits, and confirmed that the expressions of BdFer1HCH and BdFer2LCH were induced by 20-hydroecdysone, iron overload, and immune challenge.