An optimal dose-effect mode trend test for SNP genotype tables.
The genome-wide association studies have improved our understanding of the genetic basis of many complex traits. Two-by-three contingency tables are tested in these studies. The trend test for the additive mode is most often used, which is the test of 1 degree of freedom (df=1) and other tests, such as the genotype test (chi(2) (df=2)) and the chi(2) (df=1) tests for the dominant and recessive modes are also used to increase the power for markers in the non-additive modes. However, any one of them or combination of them is not perfect. We describe the relations among the chi(2) (df=2) test and chi(2) (df=1) tests for the dominant and recessive modes and the trend test for the additive mode and propose a new statistic based on their relations that tests the hypothesis that the disease-susceptible allele has a dose-effect somewhere between the recessive and dominant modes, which corresponds to the optimal dose-effect for the observed data.
Yamada
Ryo
R
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan. ryamada@src.riken.go.jp
Okada
Yukinori
Y
D000483:Alleles; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D017720:Molecular Epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide