Reliability of statistical associations between genes and disease.
Many statistical associations between a disease and alleles of specific genes have proven to be irreproducible. In part, this irreproducibility can be attributed to a lack of replication before publication and the fact that, until recently, the relationship between statistical significance and various measures of reproducibility was not widely understood. This review proposes a classification system, the Better Associations for Disease and GEnes (BADGE) system, for describing genetic associations. The BADGE classes, first class through fifth class, are based on the P value of the association. A first-class association, with P < 2 x 10(-7), is expected to be reproducible even in the absence of other evidence supporting the association. A fifth-class association corresponds to conventional statistical significance (P < 5 x 10(-2)), which provides almost no assurance of reproducibility. Three intervening classes, described as second-, third-, and fourth-class associations, are defined by P values separated by factors of 20 or 25 from these extremes.
Manly
Kenneth F
KF
Pathology and Laboratory Medicine, Anatomy and Neurobiology, Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, USA. kmanly@tennessee.edu
D000818:Animals; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D017408:Guidelines as Topic; D006801:Humans; D015203:Reproducibility of Results; D013223:Statistics as Topic