Weighted Selection Probability to Prioritize Susceptible Rare Variants in Multi-Phenotype Association Studies with Application to a Soybean Genetic Data Set.

Abstract

Rare variant association studies with multiple traits or diseases have drawn a lot of attention since association signals of rare variants can be boosted if more than one phenotype outcome is associated with the same rare variants. Most of the existing statistical methods to identify rare variants associated with multiple phenotypes are based on a group test, where a pre-specified genetic region is tested one at a time. However, these methods are not designed to locate susceptible rare variants within the genetic region. In this article, we propose new statistical methods to prioritize rare variants within a genetic region when a group test for the genetic region identifies a statistical association with multiple phenotypes. It computes the weighted selection probability (WSP) of individual rare variants and ranks them from largest to smallest according to their WSP. In simulation studies, we demonstrated that the proposed method outperforms other statistical methods in terms of true positive selection, when multiple phenotypes are correlated with each other. We also applied it to our soybean single nucleotide polymorphism (SNP) data with 13 highly correlated amino acids, where we identified some potentially susceptible rare variants in chromosome 19.