A principal components regression approach to multilocus genetic association studies

With the rapid development of modern genotyping technology, it is becoming commonplace to genotype densely spaced genetic markers such as single nucleotide polymorphisms (SNPs) along the genome. This development has inspired a strong interest in using multiple markers located in the target region for the detection of association. We introduce a principal components (PCs) regression method for candidate gene association studies where multiple SNPs from the candidate region tend to be correlated. In this approach, the total variance in the original genotype scores is decomposed into parts that correspond to uncorrelated PCs. The PCs with the largest variances are then used as regressors in a multiple regression. Simulation studies suggest that this approach can have higher power than some popular methods. An application to CHI3L2 gene expression data confirms a significant association between CHI3L2 gene expression level and SNPs from this gene that has been previously reported by others. Genet. Epidemiol. 2008. © 2007 Wiley-Liss, Inc.