Objective Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. Methods Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. Results As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways “positive regulation of cytosolic calcium ion concentration” and “inositol phosphate-mediated signaling” and hub genes including MEF2D , TSPAN2 , PHACTR1 , TRPM8 and PRDM16 related to migraine susceptibility. Conclusion Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

中文翻译：

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偏头痛的遗传变异：荟萃分析的现场概要和系统重新分析


目的 观察性研究和 GWAS 的荟萃分析显示，许多遗传变异与偏头痛易感性相关。然而，由于荟萃分析中的随机误差，显示统计显着性的结果的值得注意性仍然值得怀疑。因此，我们进行了这一领域概要和重新分析研究，以使用贝叶斯方法评估值得注意性，希望找到真正的关联。方法 PubMed 检索将来自观察性研究和 GWAS 的相关荟萃分析纳入我们的研究中，以检查所有遗传变异与偏头痛风险之间的相关性。通过假阳性率概率（FPRP）和贝叶斯错误发现概率（BFDP）分析值得注意的关联的识别。使用值得注意的变体，通过 DAVID 在线工具进行 GO 富集分析。然后，使用STRING数据库和CytoHubba软件进行PPI网络和中心基因的构建。结果 对于观察性研究中的 8 个显着遗传变异，在先验概率为 0.001 时，没有一个变异表现出值得注意的。在 GWAS 的 47 个显着遗传变异中，有 36 个通过 FPRP 或 BFDP 在先验概率为 0.000001 时值得注意。我们进一步发现了与偏头痛易感性相关的“胞质钙离子浓度的正向调节”和“磷酸肌醇介导的信号传导”途径以及包括 MEF2D 、 TSPAN2 、 PHACTR1 、 TRPM8 和 PRDM16 在内的枢纽基因。结论 在此，我们在该领域概要中确定了几个值得注意的偏头痛易感性变异。我们希望这些数据将有助于识别新的遗传生物标志物和偏头痛的潜在治疗靶点。