Comparison of dimension reduction-based logistic regression models for case-control genome-wide association study: principal components analysis vs. partial least squares

Abstract

With recent advances in biotechnology, genome-wide association study (GWAS) has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression (LR) based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression (PC-LR), partial least squares-based logistic regression (PLS-LR), have recently gained much attention in the analysis of high dimensional genomic data. However, the performance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism (SNP) set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.

Keywords: genome-wide association study; partial least squares-based logistic regression; power; principal components analysis; type I error.