A comparison study on multivariate methods for joint-SNVs association analysis

Single nucleotide variants (SNVs) have been discovered that they play crucial roles in disease pathogenesis as genetic factors. Featured by analyzing multiple SNVs in a biological module (e.g. exon, gene, etc.) collectively, the joint-SNVs studies are increasingly attractive in genome-wide association studies (GWASs), for which extensive efforts have been devoted to pursue effective multivariate methods. In this paper, we first reviewed several main streams of existing methods and their limitations in joint-SNVs studies. Then, we introduced a recently proposed novel method, namely statistic-space boundary based test (S-space BBT) to tackle these limitations. Via computational experiments on simulation datasets, not only we figured out the applicable scenarios for the six methods in considering the effect direction and whether the single significant is involved in, but also demonstrated the strong detecting sensitivity of S-space BBT under the different conditions of odds ratio, minor allele frequency, and the linkage disequilibrium. We anticipate that our study may provide clues for multivariate method selection, and that S-space BBT may play a promising role in the joint-SNVs analysis.