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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

Authors
 Jae Hyon Park  ;  Dong Il Geum  ;  Michael Eisenhut  ;  Hans J. van der Vliet  ;  Jae Il Shin 
Citation
 Gene, Vol.685 : 170-178, 2019 
Journal Title
 Gene 
ISSN
 0378-1119 
Issue Date
2019
MeSH
Alleles ; Bayes Theorem* ; Genetic Predisposition to Disease* ; Genome-Wide Association Study*/methods ; Humans ; Neoplasm Proteins/metabolism ; Neoplasms/genetics* ; Neoplasms/metabolism ; Odds Ratio ; Polymorphism, Single Nucleotide
Keywords
BFDP ; FPRP ; GWAS ; P-value ; Polymorphism
Abstract
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0378111918310965
DOI
10.1016/j.gene.2018.10.057
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
신재일(Shin, Jae Il) ORCID logo https://orcid.org/0000-0003-2326-1820
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167601
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