Joint analysis of genetic and epigenetic data using a conditional autoregressive model.

BACKGROUND

Rapidly evolving high-throughput technology has made it cost-effective to collect multilevel omic data in clinical and biological studies. Different types of omic data collected from these studies provide both shared and complementary information, and can be integrated into association analysis to enhance the power of identifying novel disease-associated biomarkers. To model the joint effect of genetic markers and DNA methylation on the phenotype of interest, we propose a joint conditional autoregressive (JCAR) model. A linear score test is used for hypothesis testing and the corresponding p value can be obtained using the Davies method.

RESULTS

The JCAR model was applied to the GAW20 data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. In our application of the JCAR model, we consider a baseline model and a full model. In the baseline model, we consider 3 different scenarios: a model with only genetic information, a model with only DNA methylation information at visit 2, and a model using both genetic and DNA methylation information at visit 2. For the full model, we consider both genetic and DNA methylation information at visit 2 and visit 4. The top 10 significant genes are reported for each model. Based on the results, we found that the gene MYO3B was significant as long as the methylation information was considered in the analysis.

CONCLUSIONS

JCAR is a useful tool for joint association analysis of genetic and epigenetic data. It is easy to implement and is computationally efficient. It can also be extended to analyze other types of omic data.