A novel gene-set association test based on variance-gamma distribution

Stat Methods Med Res. 2019 Sep;28(9):2868-2875. doi: 10.1177/0962280218791205. Epub 2018 Jul 30.

Abstract

Several gene- or set-based association tests have been proposed recently in the literature. Powerful statistical approaches are still highly desirable in this area. In this paper we propose a novel statistical association test, which uses information of the burden component and its complement from the genotypes. This new test statistic has a simple null distribution, which is a special and simplified variance-gamma distribution, and its p-value can be easily calculated. Through a comprehensive simulation study, we show that the new test can control type I error rate and has superior detecting power compared with some popular existing methods. We also apply the new approach to a real data set; the results demonstrate that this test is promising.

Keywords: Burden test; SKAT; genetic association; variance-gamma distribution.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Computer Simulation
  • Genetic Association Studies / methods*
  • Genetic Association Studies / statistics & numerical data*
  • Genotype
  • Humans
  • Models, Genetic*
  • Models, Statistical*
  • Phenotype
  • Polymorphism, Single Nucleotide