The American Society of Human Genetics, 72:1323–1330, 2003

Abstracts to publications by Rosetta Inpharmatics employees are available below. In some cases, supporting data is also available. Note: Current Rosetta Inpharmatics employees are shown in boldface type.

Peter Kraft,¹ Eric Schadt,⁴ Jason Aten,² and Steve Horvath¹,³

Abstract

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.

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Departments of ¹Biostatistics, ²Biomathematics, and ³Human Genetics, University of California at Los Angeles, Los Angeles; and ⁴Department of Research Genetics, Rosetta Inpharmatics, Seattle

Address for correspondence and reprints: Dr. Peter Kraft, UCLA School of Public Health, Box 951772, Los Angeles, CA 90095-1772. E-mail: pkraft@ucla.edu