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Supplementary Material for: Parsing the Effects of Individual SNPs in Candidate Genes with Family Data

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posted on 04.12.2009, 00:00 by Hoffmann T.J., Lange C., Vansteelandt S., Raby B.A., DeMeo D.L., Silverman E.K., Weiss S.T., Laird N.M.
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.