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Genetic model misspecification in genetic association studies #MMPMID29115983
Gaye A; Davis SK
BMC Res Notes 2017[]; 10 (ä): ä PMID29115983show ga
Objective: The underlying model of the genetic determinant of a trait is generally not known with certainty a priori. Hence, in genetic association studies, a dominant model might be erroneously modelled as additive, an error investigated previously. We explored this question, for candidate gene studies, by evaluating the sample size required to compensate for the misspecification and improve inference at the analysis stage. Power calculations were carried out with (1) the true dominant model and (2) the incorrect additive model. Empirical power, sample size and effect size were compared between scenarios (1) and (2). In each of the scenarios the estimates were evaluated for a rare (minor allele frequency < 0.01), low frequency (0.01 ? minor allele frequency < 0.05) and common (minor allele frequency ? 0.05) single nucleotide polymorphism. Results: The results confirm the detrimental effect of the misspecification error on power and effect size for any minor allele frequency. The implications of the error are not negligible; therefore, candidate gene studies should consider the more conservative sample size to compensate for the effect of error. When it is not possible to extend the sample size, methods that help mitigate the impact of the error should be systematically used. Electronic supplementary material: The online version of this article (10.1186/s13104-017-2911-3) contains supplementary material, which is available to authorized users.
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BMC+Res+Notes 2017 ; 10 (ä): ä
