title: Nonparametric tests of associations with disease based on U-statistics.
abstract: In case-control studies, association analysis was designed to test whether genetic variants were associated with human diseases. To evaluate the association, analysing one genetic marker at a time suffered from weak power, because of the correction for multiple testing and possibly small genetic effects. An alternative strategy was to test simultaneous effects of multiple markers, which was believed to be more powerful. However, when the number of markers under investigation was large, they would be subjected to weak power as well, because of the greater degrees of freedom. To conquer these limitations in case-control studies, we proposed a novel method that could test joint association of several loci (i.e. haplotype), with only a single degree of freedom. In this research, we developed a nonparametric approach, which was based on U-statistics. We also introduced a new kernel for U-statistic, which could combine the haplotype structure information, and was expected to enhance the power. Simulations indicated that our proposed approach offered merits in identifying the associations between diseases and haplotypes. Application of our method to a study of candidate genes for internalising disorder illustrated its virtue in utility and interpretation, and provided an excellent result in detecting the associations.
authors: Key Laboratory for Applied Statistics of MOE and School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, 130024, China; School of Public Health, Jilin University, Changchun, Jilin, 130021, China.
authors: Lina
authors: L
authors: Jin
authors: Wensheng
authors: W
authors: Zhu
authors: Yaqin
authors: Y
authors: Yu
authors: Changgui
authors: C
authors: Kou
authors: Xiangfei
authors: X
authors: Meng
authors: Yuchun
authors: Y
authors: Tao
authors: Jianhua
authors: J
authors: Guo
mesh_terms: D016022:Case-Control Studies; D003198:Computer Simulation; D004194:Disease / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical
chemical_list: D005819:Genetic Markers
keywords: Case-control studies; U-statistic; haplotype-based association; internalising disorder; kernel function