title: Collapsing SNP genotypes in case-control genome-wide association studies increases the type I error rate and power.
abstract: Genome-wide association studies are now widely used tools to identify genes and/or regions which may contribute to the development of various diseases. With case-control data a 2x3 contingency table can be constructed for each SNP to perform genotype-based tests of association. An increasingly common technique to increase the power to detect an association is to collapse each 2x3 table into a table assuming either a dominant or recessive mode of inheritance (2x2 table). We consider three different methods of determining which genetic model to choose and show that each of these methods of collapsing genotypes increases the type I error rate (i.e., the rate of false positives). However, one of these methods does lead to an increase in power compared with the usual genotype- and allele-based tests for most genetic models.
authors.affiliation: Rockefeller University, USA. amatthews@rockefeller.edu
authors.forename: Abigail G
authors.initials: AG
authors.lastname: Matthews
authors.forename: Chad
authors.initials: C
authors.lastname: Haynes
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data*; D020641:Polymorphism, Single Nucleotide; D012107:Research Design