The impact of imprecisely measured covariates on estimating gene-environment interactions

We investigate these effects using simulated data and illustrate our results with a practical example in nutrition epidemiology.We show that the interaction regression coefficient is unchanged by confounder measurement error under certain conditions, but biased by exposure measurement error. We also confirm that confounder measurement error can lead to estimated effects of exposure biased either towards or away from the null, depending on the correlation structure, with associated effects on type II errors.Whilst measurement error in confounders does not lead to bias in interaction coefficients, it may still lead to bias in the estimated effects of exposure. There may still be cost implications for epidemiological studies that need to calibrate all error-prone covariates against a valid reference, in addition to the exposure, to reduce the effects of confounder measurement error.One of the largest difficulties facing epidemiological research is that of measurement error in an exposure or relevant confounders [1-4]. Measurement error can lead to substantial bias in either direction, either diluting or exaggerating the apparent effect size [5]. There is a particular problem in the area of nutrition epidemiology where measuring long-term dietary intake is prone to error, such that most epidemiological studies in this field are subject potentially to very large biases [6,7]. An additional side-effect of measurement error is reduction in statistical power – the ability to detect a true difference of practical importance [8-11]. Whilst these effects of measurement error in exposures are well described, the effects of measurement error in confounding variables have received less attention [5,12-16].The source of measurement error may occur in the assessment tool used to determine the extent of exposure or dietary confounder. For example, food frequency questionnaires may use crude measures of portion size, frequency of consumption, and use broad food groupings, which all l