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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.

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