Title: Parsing the effects of individual SNPs in candidate genes with family data.
Authors: Hoffmann, Thomas J; Lange, Christoph; Vansteelandt, Stijn; Raby, Benjamin A; DeMeo, Dawn L; Silverman, Edwin K; Weiss, Scott T; Laird, Nan M
Published In Hum Hered, (2010)
Abstract: We introduce a stepwise approach for family-based designs for selecting a set of markers in a gene that are independently associated with the disease. The approach is based on testing the effect of a set of markers conditional on another set of markers. Several likelihood-based approaches have been proposed for special cases, but no model-free based tests have been proposed. We propose two types of tests in a family-based framework that are applicable to arbitrary family structures and completely robust to population stratification. We propose methods for ascertained dichotomous traits and unascertained quantitative traits. We first propose a completely model-free extension of the FBAT main genetic effect test. Then, for power issues, we introduce two model-based tests, one for dichotomous traits and one for continuous traits. Lastly, we utilize these tests to analyze a continuous lung function phenotype as a proxy for asthma in the Childhood Asthma Management Program. The methods are implemented in the free R package fbati.
PubMed ID: 19996607
MeSH Terms: Asthma/genetics*; Family; Genetic Predisposition to Disease*; Humans; Interleukin-10/genetics; Models, Genetic; Polymorphism, Single Nucleotide*; Software