Abstract
ObjectiveNumerous 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.MethodsRelevant 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.ResultsAs 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.ConclusionHerein, 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.
Highlights
Migraine is a complex and incapacitating neurologic condition with more than one billion individuals suffering from and imposes a huge socioeconomic burden worldwide [1, 2]
Studies were all selected according to the following criteria: (1) metaanalysis design study; (2) evaluating the association between genetic polymorphisms and migraine risk; (3) raw data available including odds ratios (ORs), 95% confidence intervals (CIs) or other information necessary for false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP) calculation; (4) studies published in English
Data including author, published year, genetic variant, genetic model, OR, 95% CI, P-value, ethnicity, type of migraine, number of cases and controls, heterogeneity and publication bias were extracted from the meta-analyses included according to above criteria
Summary
Migraine is a complex and incapacitating neurologic condition with more than one billion individuals suffering from and imposes a huge socioeconomic burden worldwide [1, 2]. It is characterized by recurrent episodes of unilateral throbbing pain often accompanied with nausea, phonophobia and photophobia, leading to a decline in life quality or even disability [3]. Due to the random errors in meta-analyses leading to false-positive results, the noteworthiness of the results with statistical significance remains doubtful In this field synopsis, we summarized and re-analyzed all significant genetic
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