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Diagnostic codes within electronic health record systems can vary widely in accuracy. It has been noted that the number of instances of a particular diagnostic code monotonically increases with the accuracy of disease phenotype classification. As a growing number of health system databases become linked with genomic data, it is critically important to understand the effect of this misclassification on the power of genetic association studies. Here, I investigate the impact of this diagnostic code misclassification on the power of genetic association studies with the aim to better inform experimental designs using health informatics data. The trade-off between (i) reduced misclassification rates from utilizing additional instances of a diagnostic code per individual and (ii) the resulting smaller sample size is explored, and general rules are presented to improve experimental designs.

The Impact of Diagnostic Code Misclassification on Optimizing the Experimental Design of Genetic Association Studies