Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test.
Gene-based analysis of multiple single nucleotide polymorphisms (SNPs) in a gene region is an alternative to single SNP analysis. The multi-bin linear combination test (MLC) proposed in previous studies utilizes the correlation among SNPs within a gene to construct a gene-based global test. SNPs are partitioned into clusters of highly correlated SNPs, and the MLC test statistic quadratically combines linear combination statistics constructed for each cluster. The test has degrees of freedom equal to the number of clusters and can be more powerful than a fully quadratic or fully linear test statistic. In this study, we develop a new SNP clustering algorithm designed to find cliques, which are complete subnetworks of SNPs with all pairwise correlations above a threshold. We evaluate the performance of the MLC test using the clique-based CLQ algorithm versus using the tag-SNP-based LDSelect algorithm. In our numerical power calculations we observed that the two clustering algorithms produce identical clusters about 40~60% of the time, yielding similar power on average. However, because the CLQ algorithm tends to produce smaller clusters with stronger positive correlation, the MLC test is less likely to be affected by the occurrence of opposing signs in the individual SNP effect coefficients.
Department of Mathematics Education, Seoul National University, Seoul 151-742, Republic of Korea ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea.
Yun Joo
YJ
Yoo
Department of Mathematics Education, Seoul National University, Seoul 151-742, Republic of Korea.
Sun Ah
SA
Kim
Prosserman Centre for Health Research, The Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada M5T 3L9 ; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada M5T 3M7.
Shelley B
SB
Bull
D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide