title: An efficient genome-wide association test for mixed binary and continuous phenotypes with applications to substance abuse research.
abstract: We propose a new genome-wide association test for mixed binary and continuous phenotypes that uses an efficient numerical method to estimate the empirical distribution of the Fisher's combination statistic under the null hypothesis. Our simulation study shows that the proposed method controls the type I error rate and also maintains its power at the level of the permutation method. More importantly, the computational efficiency of the proposed method is much higher than the one of the permutation method. The simulation results also indicate that the power of the test increases when the genetic effect increases, the minor allele frequency increases, and the correlation between responses decreases. The statistical analysis on the database of the Study of Addiction: Genetics and Environment demonstrates that the proposed method combining multiple phenotypes can increase the power of identifying markers that may not be, otherwise, chosen using marginal tests.
authors.affiliation: 1 Department of Health Behavior and Biological Sciences, University of Michigan, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Buu
authors.affiliation: 2 Department of Internal Medicine, Henry Ford Health System, USA.|3 The Center for Health Policy and Health Services Research, Henry Ford Health System, USA.
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
authors.affiliation: 4 School of Nursing, University of Michigan, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D056808:Biostatistics / Q000379:methods*; D003198:Computer Simulation; D030541:Databases, Genetic / Q000706:statistics & numerical data; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D009010:Monte Carlo Method; D020412:Multifactorial Inheritance; D015999:Multivariate Analysis; D010641:Phenotype; D019966:Substance-Related Disorders / Q000235:genetics*
keywords: Fisher combination function; Genome-wide association study; multivariate permutation; substance abuse