Abstract: The association study of rare genetic variants and disease traits as a supplement of genome-wide association study (GWAS) has achieved remarkable development and application. But the traditional association testing methods are not suitable for the rare variants association problem. Many new testing methods designed specifically for the rare variants have been proposed and applied. The variable-threshold (VT) method is one of them, which has achieved more power than the traditional association test methods. Here the occurrence of the mutation of rare variants was treated as a rare event. Poisson distribution was taken instead of binomial distribution and a new test statistic was proposed. Base on the VT method, a new test method was proposed, namely, the Poisson approximation variable threshold method (PAVT). Simulation results show that the new method has more power than VT method uniformly, and variant selection is more efficient.

Key words: genome-wide association study, rare variants, Poisson approximation