The Annals of Applied Statistics

Adjustment of nonconfounding covariates in case-control genetic association studies

Hong Zhang, Nilanjan Chatterjee, Daniel Rader, and Jinbo Chen

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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.

Article information

Source
Ann. Appl. Stat. Volume 12, Number 1 (2018), 200-221.

Dates
Received: May 2016
Revised: January 2017
First available in Project Euclid: 9 March 2018

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1520564470

Digital Object Identifier
doi:10.1214/17-AOAS1065

Keywords
Case-control studies Hardy–Weinberg equilibrium nonconfounding covariates profile likelihood

Citation

Zhang, Hong; Chatterjee, Nilanjan; Rader, Daniel; Chen, Jinbo. Adjustment of nonconfounding covariates in case-control genetic association studies. Ann. Appl. Stat. 12 (2018), no. 1, 200--221. doi:10.1214/17-AOAS1065. https://projecteuclid.org/euclid.aoas/1520564470


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Supplemental materials

  • Appendix. Proof of Theorems 1–2 and equations (2.13) and (2.14), Figures S1–S7, and Tables S1–S10.