Key result
The rs2651899 CC genotype (OR 1.32; 95% CI 1.02-1.73; p=0.04) and the rs10166942 CT genotype (OR 1.36; 95% CI 1.18-1.57; p<0.0001) were significantly associated with increased risk of migraine.
Why the study?
Data from studies examining the relationship between rs2651899, rs10166942, and rs11172113 polymorphisms and migraine remain inconclusive.
Do the rs2651899, rs10166942, and rs11172113 polymorphisms increase the risk of migraine?
Meta-Analysis
Do the rs2651899, rs10166942, and rs11172113 polymorphisms increase the risk of migraine?
The rs2651899 and rs10166942 polymorphisms are significantly associated with an increased risk of migraine, supporting a genetic basis for the condition.
Answers are grounded in this paper and cite their sources.
Variants in PRDM16 and TRPM8 increase migraine risk; confirms select GWAS signals but leaves replication and clinical utility open.
The genetic basis of migraine is rather complex. The rs2651899 in the PR/SET domain 16 (PRDM16) gene, the rs10166942 near the transient receptor potential cation channel subfamily M member 8 (TRPM8) gene, and the rs11172113 in the LDL receptor-related protein 1 (LRP1) gene, have been associated with migraine in a genome-wide association study (GWAS). However, data from subsequent studies examining the role of these variants and their relationship with migraine remain inconclusive. The aim of the present study was to meta-analyze the published data assessing the role of these polymorphisms in migraine, migraine with aura (MA), and migraine without aura (MO). We performed a search in the PubMed, Scopus, Web of Science, and Public Health Genomics and Precision Health Knowledge Base (v7.7) databases. In total, eight, six, and six studies were included in the quantitative analysis, for the rs2651899, rs10166942, and rs11172113, respectively. Cochran’s Q and I2 tests were used to calculate the heterogeneity. The random effects (RE) model was applied when high heterogeneity was observed; otherwise, the fixed effects (FE) model was applied. The odds ratios (ORs) and the respective 95% confidence intervals (CIs) were calculated to estimate the effect of each variant on migraine. Funnel plots were created to graphically assess publication bias. A significant association was revealed for the CC genotype of the rs2651899, with the overall migraine group (RE model OR: 1.32; 95% CI: 1.02−1.73; p-value = 0.04) and the MA subgroup (FE model OR: 1.40; 95% CI: 1.12−1.74; p-value = 0.003). The rs10166942 CT genotype was associated with increased migraine risk (FE model OR: 1.36; 95% CI: 1.18−1.57; p-value < 0.0001) and increased MO risk (FE model OR: 1.41; 95% CI: 1.17−1.69; p-value = 0.0003). No association was detected for the rs11172113. The rs2651899 and the rs10166942 have an effect on migraine. Larger studies are needed to dissect the role of these variants in migraine.
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Siokas et al. (2022) conducted a meta-analysis in Migraine. rs2651899 CC genotype was evaluated on Overall migraine risk (OR 1.32, 95% CI 1.02-1.73, p=0.04). The rs2651899 CC genotype (OR 1.32; 95% CI 1.02-1.73; p=0.04) and the rs10166942 CT genotype (OR 1.36; 95% CI 1.18-1.57; p<0.0001) were significantly associated with increased risk of migraine.
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