Bayesian linear mixed model with multiple random effects for family-based genetic studies

Abstract

Motivation: Family-based study design is one of the popular designs used in genetic research, and the whole-genome sequencing data obtained from family-based studies offer many unique features for risk prediction studies. They can not only provide a more comprehensive view of many complex diseases, but also utilize information in the design to further improve the prediction accuracy. While promising, existing analytical methods often ignore the information embedded in the study design and overlook the predictive effects of rare variants, leading to a prediction model with sub-optimal performance. Results: We proposed a Bayesian linear mixed model for the prediction analysis of sequencing data obtained from family-based studies. Our method can not only capture predictive effects from both common and rare variants, but also easily accommodate various disease model assumptions. It uses information embedded in the study design to form surrogates, where the predictive effects from unmeasured/unknown genetic and environmental risk factors can be modelled. Through extensive simulation studies and the analysis of sequencing data obtained from the Michigan State University Twin Registry study, we have demonstrated that the proposed method outperforms commonly adopted techniques. Availability: R package is available at https://github.com/yhai943/FBLMM.