title: A gene-based method for detecting gene-gene co-association in a case-control association study.
abstract: Association study (especially the genome-wide association study) now has a key function in identification and characterization of disease-predisposing genetic variant(s), which customarily involve multiple single nucleotide polymorphisms (SNPs) in a candidate region or across the genome. Case-control association design remains the most popular and a challenging issue in the statistical analysis is the optimal use of all information contained in these SNPs. Previous approaches often treated gene-gene interaction as deviation from additive genetic effects or replaced it with SNP-SNP interaction. However, these approaches are limited for their failure of consideration of gene-gene interaction or gene-gene co-association at gene level. Although the co-association of the SNPs within a candidate gene can be detected by principal component analysis-based logistic regression model, the detection of co-association between genes in genome remains uncertain. Here, we proposed a canonical correlation-based U statistic (CCU) for detecting gene-based gene-gene co-association in the case-control design. We explored its type I error rates and power through simulation and analyzed two real data sets. By treating gene as a functional unit in analysis, we found that CCU was a strong alternative to previous approaches. We discussed the performance of CCU as a gene-based gene-gene co-association statistic and the prospect of further improvement.
authors.affiliation: Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Peng
authors.forename: Jinghua
authors.initials: J
authors.lastname: Zhao
authors.forename: Fuzhong
authors.initials: F
authors.lastname: Xue
mesh_terms: D016022:Case-Control Studies; D005796:Genes / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics