The genetics of gene expression: comparison of linkage scans using two phenotype normalization methods

The goal of this paper is to investigate the effects of normalization procedures for expression data on linkage results. We selected the two most commonly used expression data extraction and normalization methods, Affymetrix global scaling and dChip invariant. After applying these two methods in 3554 expression phenotypes, we identified 45 phenotypes that were more likely to be genetic for either normalization procedure. A genome-wide linkage scan was performed on these expression values (45 phenotypes × 2 normalizations) using 2272 SNPs. Our results showed that: 1) the dChip normalization might inflate the LOD scores because the dChip normalization yielded LOD scores > 3.0 30% more frequently than the Affy normalization, and 2) the difference in LODs between the normalizations were not correlated with their heritabilities. In summary, we conclude, as have other published reports, that normalization methods play an important role in the linkage results, and that some significant linkage signals might be due to a specific normalization method.