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Open Access Research article

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

Elias Zintzaras12* and Mauro Santos3

Author Affiliations

1 Department of Biomathematics, University of Thessaly School of Medicine, 2 Panepistimiou Str, Biopolis, Larissa 41110, Greece

2 The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, 800 Washington Str, Boston, MA 02111, USA

3 Departament de Genètica i de Microbiologia, Grup de Biologia Evolutiva, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

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BMC Medical Research Methodology 2011, 11:171  doi:10.1186/1471-2288-11-171

Published: 21 December 2011

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.