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Bayesian statistical methods in genetic association studies: Empirical examination of statistically non-significant Genome Wide Association Study (GWAS) meta-analyses in cancers: A systematic review

Park, Jae Hyon, Geum, Dong Il, Eisenhut, Michael, van der Vliet, Hans J., Shin, Jae Il
Gene 2019 v.685 pp. 170-178
Bayesian theory, confidence interval, gene frequency, genome, genome-wide association study, humans, meta-analysis, neoplasms, observational studies, odds ratio, research institutions, single nucleotide polymorphism, systematic review, t-test
A Bayesian statistical method was developed to assess the noteworthiness of a single nucleotide polymorphism (SNP)-phenotype association that shows statistical significance in various observational studies, but it has seldom been applied to GWAS meta-analyses in cancers. Data (i.e. allelic frequency, odds ratio, 95% confidence interval, etc.) on various SNP-cancer associations were extracted from meta-analysis of GWAS and the National Human Genome Research Institute (NHGRI) Catalog of Published GWAS and were used to compute the false positive report probability (FPRP) and Bayesian false discovery probability (BFDP) to evaluate the noteworthiness of SNP-cancer associations. Independent paired t-tests showed a direct relationship between SNP-cancer P-values and both FPRP and BFDP estimates. However, a discrepancy in the number of noteworthy associations between P-value comparison and either FPRP or BFDP was found using data extracted from meta-analyses of GWAS and the GWAS Catalog. Most P-values of associations with nonsignificant P-values but with noteworthy FPRP and BFDP estimates were within the range of 10−6 to 5 × 10−8. A poorly selected genome-wide significance threshold and inclusion of a nonsignificant SNP-phenotype association into the noteworthy test can, with either noteworthy FPRP or BFDP computation, give a false impression of noteworthiness for a nonsignificant association.