Department of Neurology, First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, Liaoning, China.
J Headache Pain. 2020 Feb 11;21(1):13. doi: 10.1186/s10194-020-01087-5.
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.
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.
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.
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.
大量来自观察性研究荟萃分析和 GWAS 的遗传变异被报道与偏头痛易感性相关。然而，由于荟萃分析中的随机误差，显示统计学显著的结果的重要性仍然值得怀疑。因此，我们采用贝叶斯方法进行了这项领域综述和再分析研究，以评估使用有意义性，希望能找到真正的关联。
通过 PubMed 搜索，我们将观察性研究和 GWAS 中检查所有遗传变异与偏头痛风险之间相关性的相关荟萃分析纳入本研究。通过假阳性率概率（FPRP）和贝叶斯假发现概率（BFDP）分析显著关联的有意义性。使用有意义的变异，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 网络和枢纽基因分析。
对于 8 个来自观察性研究的显著遗传变异，在先前概率为 0.001 的情况下，没有一个显示有意义性。在 47 个 GWAS 中的显著遗传变异中，通过 FPRP 或 BFDP，有 36 个在先前概率为 0.000001 时具有有意义性。我们进一步发现了与偏头痛易感性相关的途径“细胞质钙离子浓度的正调节”和“肌醇磷酸盐介导的信号转导”，以及枢纽基因包括 MEF2D、TSPAN2、PHACTR1、TRPM8 和 PRDM16。
在本综述中，我们已经确定了几个与偏头痛易感性相关的有意义的变异。我们希望这些数据有助于确定偏头痛的新型遗传生物标志物和潜在治疗靶点。
