Extension of Within-Family Genetic Association to Polytomous Phenotypes and Two-Locus Models

• Activity Number: 311
• Type: Contributed
• Date/Time: Tuesday, August 6, 2013 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Alexandre Bureau*+ and Jordie Croteau and Thierry Duchesne
• Companies: Université Laval and Institut universitaire en santé mentale de Québec and Université Laval
• Keywords: conditional likelihood ; complex traits ; , robust variance estimation ; score test

Abstract

In familial genetic association studies of dichotomous phenotypes, inference is often performed using within-family information to guard against potential bias due to the genetic structure of the population. We extend the usual logistic model between a dichotomous phenotype and an allele count in two ways: polytomous phenotype with K>2 levels, and modelling of allele counts X at two unlinked marker loci. Inference on parameters of the model is performed in extended pedigrees using two approaches: score tests taking into account the correlation between relatives in the entire pedigree as previously proposed in the Generalized Disequilibrium Test and estimation under a conditional likelihood for nuclear families, with an empirical estimator of the variance of the parameter estimates robust to dependence between nuclear families belonging to the same pedigree. Simulations confirm that the tests and estimates have the expected statistical properties. The methods were applied to candidate genetic markers, cognitive endophenotypes and schizophrenia and bipolar disorder in large kindreds from Eastern Quebec.