Abstract
It has recently been reported that adjustment of nonconfounding covariates in case-control genetic association analyses may lead to decreased power when the phenotype is rare. This observation contrasts a well-known result for clinical trials where adjustment of baseline variables always leads to increased power for testing randomized treatment effects. In this paper, we propose a unified solution that guarantees increased power through covariate adjustment regardless of whether the phenotype is rare or common. Our method exploits external phenotype prevalence data through a profile likelihood function, and can be applied to fit any commonly used penetrance models including the logistic and probit regression models. Through extensive simulation studies, we showed empirically that the power of our method was indeed higher than available analysis strategies with or without covariate adjustment, and can be considerably higher when the phenotype was common and the covariate effect was strong. We applied the proposed method to analyze a case-control genetic association study on human high density lipoprotein cholesterol level.
Original language | English (US) |
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Pages (from-to) | 200-221 |
Number of pages | 22 |
Journal | Annals of Applied Statistics |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - Mar 2018 |
Keywords
- Case-control studies
- Hardy
- Nonconfounding covariates
- Profile likelihood
- Weinberg equilibrium
ASJC Scopus subject areas
- Statistics and Probability
- Modeling and Simulation
- Statistics, Probability and Uncertainty