For further replicate these findings, we selected two SNPs; rs2651899 on chromosome 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population.
TRPM8 is expressed on sensory afferents innervating the meninges, and these neurons are subject to developmental changes that may influence their contribution to migraine.
Recent genome-wide association studies (GWAS) have identified 3 loci in or near PRDM16 (1p36.32, rs2651899), LRP1 (12q13.3, rs11172113) and TRPM8 (2q37.1, rs10166942) in the population-based Women's Genome Health Study (WGHS) of migraine, and 2 loci in or near TRPM8 and LRP1 were repeated in European GWAS study.
To further replicate the GWAS findings, we investigated the 3 variants rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8), and rs11172113 (12q13.3, LRP1) for their association with migraine in the Chinese Han population.
On the other hand, TRPM8rs10166942 and TGFBR2 rs7640543 variants did not have significant influence on migraine susceptibility in the North Indian population.
Two out of three SNPs that showed genome-wide significant associations in the previous study: rs10166942 (near TRPM8) and rs11172113 (in LRP1) were significantly associated with migraine in the present study.
TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.
In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine.