statistical distributions of test statistics used for quantitative trait association mapping in structured populations统计分布的测试统计数据用于定量特征关联映射在结构化种群.pdf

Teyssèdre et al. Genetics Selection Evolution 2012, 44:32 Ge n e t i c s /content/44/1/32 Se l e c t i o n Evolution RESEARCH Open Access Statistical distributions of test statistics used for quantitative trait association mapping in structured populations 1 1 2* Simon Teyssèdre , Jean-Michel Elsen and Anne Ricard Abstract Background: Spurious associations between single nucleotide polymorphisms and phenotypes are a major issue in genome-wide association studies and have led to underestimation of type 1 error rate and overestimation of the number of quantitative trait loci found. Many authors have investigated the influence of population structure on the robustness of methods by simulation. This paper is aimed at developing further the algebraic formalization of power and type 1 error rate for some of the classical statistical methods used: simple regression, two approximate methods of mixed models involving the effect of a single nucleotide polymorphism (SNP) and a random polygenic effect (GRAMMAR and FASTA) and the transmission/disequilibrium test for quantitative traits and nuclear families. Analytical formulae were derived using matrix algebra for the first and second moments of the statistical tests, assuming a true mixed model with a polygenic effect and SNP effects. Results: The expectation and variance of the test statistics and their marginal expectations and variances according to the distribution of genotypes and estimators of variance components are given a