Communications for Statistical Applications and Methods

The Korean Statistical Society (한국통계학회)
권호 표지
DOI QR코드

DOI QR Code

Statistical Bias and Inflated Variance in the Genehunter Nonparametric Linkage Test Statistic

  • Published : 2009.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Evidence of linkage is expressed as a decreasing trend of the squared trait difference of two siblings with increasing identical by descent scores. In contrast to successes in the application of a parametric approach of Haseman-Elston regression, notably low powers are demonstrated in the nonparametric linkage analysis methods for complex traits and diseases with sib-pairs data. We report that the Genehunter nonparametric linkage statistic is biased and furthermore the variance formula that they used is an inflated one, and this is one reason for a low performance. Thus, we propose bias-corrected nonparametric linkage statistics. Simulation studies comparing our proposed nonparametric test statistics versus the existing test statistics suggest that the bias-corrected new nonparametric test statistics are more powerful and attains efficiencies close to that of Haseman-Elston regression.

Keywords

References

  1. Abecasis, G., Cox, N., Daly, M. J., Kruglyak, L., Laird, N., Markianos, K. and Patterson, N. (2004). No bias in linkage analysis, The American Journal of Human Genetics, 75, 722-723 https://doi.org/10.1086/424757
  2. Davis, S. and Weeks, D. E. (1997). Comparison of nonparametric statistics for detection of linkage in nuclear families: Single-marker evaluation, The American Journal of Human Genetics, 61, 1431-1444 https://doi.org/10.1086/301635
  3. Fernandez, J. R., Etzel, C., Beasley, T. M., Shete, S., Amos, C. I. and Allison, D. B. (2002). Improv-ing the power of sib-pair quantitative trait loci detection by phenotype winsorization, Human Heredity, 53, 59-67 https://doi.org/10.1159/000057984
  4. Hadicke, O., Pahlke, F. and Ziegler, A. (2008). A general approach for sample size and power calculations based on the Haseman-Elston method, Biometrical Journal, 50, 257-269 https://doi.org/10.1002/bimj.200710404
  5. Haseman, J. K. and Elston, R. C. (1972). The investigation of linkage between a quantitative trait and a marker locus, Behavioral Genetics, 2, 3-19 https://doi.org/10.1007/BF01066731
  6. Hettmansperger, T. P. (1984). Statictical Inference Based on Ranks, John Wiley & Sons, New York
  7. Jonckheere, A. R. (1954). A distribution-free k-sample test against ordered alternatives, Biometrika, 41, 133-145 https://doi.org/10.1093/biomet/41.1-2.133
  8. Kim, M. K., Hong, Y. J. and Song, H. H. (2006). Nonparametric trend statistic incorporating disper-sion differences in sib pair linkage for quantitative traits, Human Heredity, 62, 1-11 https://doi.org/10.1159/000095597
  9. Kruglyak, L. and Lander, E. S. (1995). Complete multipoint sib-pair analysis of qualitative and quan-titative traits, The American Journal of Human Genetics, 57, 439-454
  10. Mukhopadhyay, I., Feingold, E. and Weeks, D. E. (2004). No “Bias” toward the null hypothesis in most conventional multipoint nonparametric linkage analysis, The American Journal of Human Genetics, 75, 716-718 https://doi.org/10.1086/424754
  11. Schork, N. J. and Greenwood, T. A. (2004a). Inherent bias toward the null hypothesis in conventional multipoint nonparametric linkage analysis, The American Journal of Human Genetics, 74, 306-316 https://doi.org/10.1086/381714
  12. Schork, N. J. and Greenwood, T. A. (2004b). Got bias? the authors reply, The American Journal of Human Genetics, 75, 723-727 https://doi.org/10.1086/424758
  13. Sieberts, S. K., Broman, K. W. and Gudbjartsson, D. F. (2004). “Bias toward the null” means reduced power, The American Journal of Human Genetics, 75, 720-722 https://doi.org/10.1086/424756
  14. Terpstra, T. J. (1952). The asymptotic normality and consistency of Kendall's test against trend, when ties are present in one ranking, Indagationes Mathematicae, 14, 327-333
  15. Visscher, P. M. and Wray, N. R. (2004). Conventional multipoint nonparametric linkage analysis is not necessarily inherently biased, The American Journal of Human Genetics, 75, 718-720 https://doi.org/10.1086/424755