Nonparametric Tests of Associations with Disease Based on U-Statistics

Authors

  • Lina Jin,

    1. Key Laboratory for Applied Statistics of MOE and School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, China
    2. School of Public Health, Jilin University, Changchun, Jilin, China
    Search for more papers by this author
  • Wensheng Zhu,

    1. Key Laboratory for Applied Statistics of MOE and School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, China
    Search for more papers by this author
  • Yaqin Yu,

    1. School of Public Health, Jilin University, Changchun, Jilin, China
    Search for more papers by this author
  • Changgui Kou,

    1. School of Public Health, Jilin University, Changchun, Jilin, China
    Search for more papers by this author
  • Xiangfei Meng,

    1. School of Public Health, Jilin University, Changchun, Jilin, China
    Search for more papers by this author
  • Yuchun Tao,

    Corresponding author
    1. School of Public Health, Jilin University, Changchun, Jilin, China
    • Corresponding authors: Dr. Jianhua Guo, School of Mathematics and Statistics, Northeast Normal University, 5268 Renmin Street, Changchun 130024, P.R. China. Tel: +86 431 85098576; Fax: +86 431 85098237; E-mail: jhguo@nenu.edu.cn and

      Dr. Yuchun Tao, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, P.R. China. Tel: +86 431 85619456; E-mail: tyc@jlu.edu.cn

    Search for more papers by this author
  • Jianhua Guo

    Corresponding author
    1. Key Laboratory for Applied Statistics of MOE and School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, China
    • Corresponding authors: Dr. Jianhua Guo, School of Mathematics and Statistics, Northeast Normal University, 5268 Renmin Street, Changchun 130024, P.R. China. Tel: +86 431 85098576; Fax: +86 431 85098237; E-mail: jhguo@nenu.edu.cn and

      Dr. Yuchun Tao, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun 130021, P.R. China. Tel: +86 431 85619456; E-mail: tyc@jlu.edu.cn

    Search for more papers by this author

Summary

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.

Ancillary