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Genetic model misspecification in genetic association studies
#MMPMID29115983
Gaye A
; Davis SK
BMC Res Notes
2017[Nov]; 10
(1
): 569
PMID29115983
show 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.
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