title: Poisson Approximation-Based Score Test for Detecting Association of Rare Variants.
abstract: Genome-wide association study (GWAS) has achieved great success in identifying genetic variants, but the nature of GWAS has determined its inherent limitations. Under the common disease rare variants (CDRV) hypothesis, the traditional association analysis methods commonly used in GWAS for common variants do not have enough power for detecting rare variants with a limited sample size. As a solution to this problem, pooling rare variants by their functions provides an efficient way for identifying susceptible genes. Rare variant typically have low frequencies of minor alleles, and the distribution of the total number of minor alleles of the rare variants can be approximated by a Poisson distribution. Based on this fact, we propose a new test method, the Poisson Approximation-based Score Test (PAST), for association analysis of rare variants. Two testing methods, namely, ePAST and mPAST, are proposed based on different strategies of pooling rare variants. Simulation results and application to the CRESCENDO cohort data show that our methods are more powerful than the existing methods.
authors.affiliation: Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, 230026, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Fang
authors.affiliation: Institute of Biostatistics, Fudan School of Life Sciences, Fudan, Shanghai, 200433, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, 230026, China.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Yang
mesh_terms: D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D016012:Poisson Distribution
keywords: Genome-wide association study; Poisson approximation; rare variants