Parsing the effects of individual SNPs in candidate genes with family data.
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.
Hoffmann
Thomas J
TJ
Department of Biostatistics, Harvard School of Public Health, Boston, Mass. 02115, USA. tjhoffm@gmail.com
Lange
Christoph
C
Vansteelandt
Stijn
S
Raby
Benjamin A
BA
DeMeo
Dawn L
DL
Silverman
Edwin K
EK
Weiss
Scott T
ST
Laird
Nan M
NM
D001249:Asthma / Q000235:genetics*; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012984:Software
C508609:IL10 protein, human; D016753:Interleukin-10