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Reliability of statistical associations between genes and disease

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Abstract

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<2×10−7, 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<5×10−2), 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.

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Acknowledgements

The author is pleased to acknowledge many helpful comments from an anonymous reviewer, support from the Center of Excellence for Genomics and Bioinformatics of the University of Tennessee Health Science Center, and grants HG001656-06, CA105417-01, and MH62009-05 from the National Institutes of Health.

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  1. Pathology and Laboratory Medicine, Anatomy and Neurobiology, Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN, USA

    Kenneth F. Manly

  2. Biostatistics, University at Buffalo, Buffalo, NY, USA

    Kenneth F. Manly

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Manly, K.F. Reliability of statistical associations between genes and disease. Immunogenetics 57, 549–558 (2005). https://doi.org/10.1007/s00251-005-0025-x

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