Collaborative Phenotype Inference from Comorbid Substance Use Disorders and Genotypes.

Abstract

Data in large-scale genetic studies of complex human diseases, such as substance use disorders, are often incomplete. Despite great progress in genotype imputation, e.g., the IMPUTE2 method, considerably less progress has been made in inferring phenotypes. We designed a novel approach to integrate individuals' comorbid conditions with their genotype data to infer missing (unreported) diagnostic criteria of a disorder. The premise of our approach derives from correlations among symptoms and the shared biological bases of concurrent disorders such as co-dependence on cocaine and opioids. We describe a matrix completion method to construct a bi-linear model based on the interactions of genotypes and known symptoms of related disorders to infer unknown values of another set of symptoms or phenotypes. An efficient stochastic and parallel algorithm based on the linearized alternating direction method of multipliers was developed to solve the proposed optimization problem. Empirical evaluation of the approach in comparison with other advanced data matrix completion methods via a case study shows that it both significantly improves imputation accuracy and provides greater computational efficiency.