Primary analysis of case–control studies focuses on the relationship between disease D and a set of covariates of interest (Y, X). A secondary application of the case–control study, which is often invoked in modern genetic epidemiologic association studies, is to investigate the interrelationship between the covariates themselves. The task is complicated owing to the case–control sampling, where the regression of Y on X is different from what it is in the population. Previous work has assumed a parametric distribution for Y given X and derived semiparametric efficient estimation and inference without any distributional assumptions about X. We take up the issue of estimation of a regression function when Y given X follows a homoscedastic regression model, but otherwise the distribution of Y is unspecified. The semiparametric efficient approaches can be used to construct semiparametric efficient estimates, but they suffer from a lack of robustness to the assumed model for Y given X. We take an entirely different approach. We show how to estimate the regression parameters consistently even if the assumed model for Y given X is incorrect, and thus the estimates are model robust. For this we make the assumption that the disease rate is known or well estimated. The assumption can be dropped when the disease is rare, which is typically so for most case–control studies, and the estimation algorithm simplifies. Simulations and empirical examples are used to illustrate the approach.
We study the regression relationship between covariates in case–control data: an area known as the secondary analysis of case–control studies. The context is such that only the form of the regression mean is specified, so that we allow an arbitrary regression error distribution, which can depend on the covariates and thus can be heteroscedastic. Under mild regularity conditions we establish the theoretical identifiability of such models. Previous work in this context has either specified a fully parametric distribution for the regression errors, specified a homoscedastic distribution for the regression errors, has specified the rate of disease in the population (we refer to this as the true population) or has made a rare disease approximation. We construct a class of semiparametric estimation procedures that rely on none of these. The estimators differ from the usual semiparametric estimators in that they draw conclusions about the true population, while technically operating in a hypothetical superpopulation. We also construct estimators with a unique feature, in that they are robust against the misspecification of the regression error distribution in terms of variance structure, whereas all other non-parametric effects are estimated despite the biased samples. We establish the asymptotic properties of the estimators and illustrate their finite sample performance through simulation studies, as well as through an empirical example on the relationship between red meat consumption and hetero-cyclic amines. Our analysis verified the positive relationship between red meat consumption and two forms of hetro-cyclic amines, indicating that increased red meat consumption leads to increased levels of MeIQx and PhIP, both being risk factors for colorectal cancer. Computer software as well as data to illustrate the methodology are available from http://www.stat.tamu.edu/~carroll/matlab__programs/software.php .
more » « less- PAR ID:
- 10397455
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Journal of the Royal Statistical Society Series B: Statistical Methodology
- Volume:
- 78
- Issue:
- 1
- ISSN:
- 1369-7412
- Page Range / eLocation ID:
- p. 127-151
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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