A family-based test for correlation between gene expression and trait values.
Advances in microarray technology have made it attractive to combine information on clinical traits, marker genotypes, and comprehensive gene expression from family studies to dissect complex disease genetics. Without accounting for family structure, methods that test for association between a trait and gene-expression levels can be misleading. We demonstrate that the standard unstratified test based on Pearson's correlation coefficient can produce spurious results when applied to family data, and we present a stratified family expression association test (FEXAT). We illustrate the utility of the FEXAT via simulation and an application to gene-expression data from lymphoblastoid cell lines from four CEPH families. The FEXAT has a smaller estimated false-discovery rate than the standard test when within-family correlations are of interest, and it detects biologically plausible correlations between beta catenin and genes in the WNT-activation pathway in humans that the standard test does not.
Kraft
Peter
P
Department of Biostatistics, University of California at Los Angeles, Los Angeles, CA 90095-1772, USA. pkraft@ucla.edu
Schadt
Eric
E
Aten
Jason
J
Horvath
Steve
S
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D003198:Computer Simulation; D003598:Cytoskeletal Proteins / Q000235:genetics; D005189:False Positive Reactions; D005190:Family; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008214:Lymphocytes; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics; D035781:Siblings; D013223:Statistics as Topic / Q000379:methods*; D015534:Trans-Activators / Q000235:genetics; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin