Bayesian detection of causal rare variants under posterior consistency.
Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.
Department of Statistics, Texas A&M University, College Station, Texas, United States of America. fliang@stat.tamu.edu
Faming
F
Liang
Momiao
M
Xiong
D000465:Algorithms; D001499:Bayes Theorem; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D003198:Computer Simulation; D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008957:Models, Genetic; D009203:Myocardial Infarction / Q000235:genetics; D012372:ROC Curve; D017422:Sequence Analysis, DNA; D013997:Time Factors