Estimating the mode of inheritance in genetic association studies of qualitative traits based on the degree of dominance index

Elias Zintzaras, Mauro Santos

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30 Citations (Scopus)

Abstract

Background: The biological justification for the choice of the genetic mode in genetic association studies (GAS) is seldom available. Then, the mode of inheritance is approximated by investigating a number of non-orthogonal genetic contrasts making the interpretation of results difficult. Methods. We propose to define the mode of inheritance by the significance of the deviance of the co-dominant contrast and the degree of dominance (h), which is a function of two orthogonal contrasts (the co-dominant and additive). Non-dominance exists when the co-dominant contrast is non-significant and, hence, the risk effect of heterozygotes lies in the middle of the risk of the two homozygotes. Otherwise, dominance (including over- and under-dominance) is present and the direction of dominance depends on the value of h. Results: Simulations show that h may capture the real mode of inheritance and it is affected by deviations from Hardy-Weinberg equilibrium (HWE). In addition, power for detecting significance of h when the study conforms to HWE rule increases with the degree of dominance and to some extent is related to the mutant allele frequency. Conclusion: The introduction of the degree of dominance provides useful insights into the mode of inheritance in GAS. © 2011 Zintzaras and Santos; licensee BioMed Central Ltd.
Original languageEnglish
Article number171
JournalBMC Medical Research Methodology
Volume11
DOIs
Publication statusPublished - 22 Dec 2011

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