Testing for Genetic Interactions in Complex Disease With Distance Correlation

ABSTRACT Understanding epistasis (genetic interaction) may shed some light on the genomic basis of common diseases, including disorders of maximum interest due to their high socioeconomic burden, like schizophrenia. Distance correlation is an association measure that characterizes general statistical independence between random variables, not only the linear one. Here, we propose distance correlation as a novel tool for the detection of epistasis from case‐control data of single‐nucleotide polymorphisms. On the methodological side, we highlight the derivation of the explicit asymptotic null distribution of the test statistic. We show that this is the only way to obtain enough computational speed for the method to be used in practice, in a scenario where the resampling techniques found in the literature are impractical. Our simulations show satisfactory calibration of significance, as well as comparable or better power than existing methodology. We conclude with the application of our technique to a schizophrenia genetics dataset, obtaining biologically sound insights.