Adjustment of nonconfounding covariates in case-control genetic association studies

Hong Zhang, Nilanjan Chatterjee, Daniel Rader, Jinbo Chen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 languageEnglish (US)
Pages (from-to)200-221
Number of pages22
JournalAnnals of Applied Statistics
Issue number1
StatePublished - Mar 2018


  • Case-control studies
  • Hardy
  • Nonconfounding covariates
  • Profile likelihood
  • Weinberg equilibrium

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Statistics, Probability and Uncertainty


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