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다변량 형질의 유전연관성에 대한 주성분을 이용한 회귀방법와 다변량 비모수 추세검정법의 비교

Comparison of Principal Component Regression and Nonparametric Multivariate Trend Test for Multivariate Linkage

  • 김수영 (가톨릭대학교 의학통계학과) ;
  • 송혜향 (가톨릭대학교 의학통계학과)
  • Kim, Su-Young (Dept. of Biostatistics, The Catholic University of Korea) ;
  • Song, Hae-Hiang (Dept. of Biostatistics, The Catholic University of Korea)
  • 발행 : 2008.02.29

초록

연속 형질(quantitative trait)에 영향을 미치는 유전자를 알아내기 위해 형제 쌍의 자료를 수집하여, 주로 이용되는 Haseman과 Elston (1972)의 최소제곱 회귀검정법으로 분석하는데 이는 단일 형질에 대한 분석법이다. 현실적으로 여러 형질들이 복잡하게 단일유전자 좌위(single locus)와 연관되어 있어 함께 수집하게 되는 경우에는, 이러한 연관된 여러 형질을 동시에 분석하는 유전연관성 검정법(linkage test)이 절실히 필요한 실정이다. Amos 등 (1990)은 주성분(principal component) 선형모형을 이용하여 Haseman과 Elston (1972)방법을 둘 이상의 형질의 다변량 분석법으로 확장시켰다. 그러나 이 검정방법은 통계량의 분포를 알 수 없기에 아직 제 1종 오류가 제대로 통제되지 못하는 문제를 가지고 있다. 본 논문에서는 이러한 다변량 형질 자료의 연관성검정에 있어 단일변량에 대한 비모수 추세검정법을 다변량 자료에 대한 분석법으로 확장시킨 통계량을 사용할 것을 제안한다. Amos 등 (1990)이 제안한 방법과 다변량 추세검정 통계량을 모의실험으로 생성한 연속형 형질자료에 적용하였을 때, 다변량 추세검정 통계량은 Amos 등 (1990) 방법에서의 여러 문제점이 발생되지 않을 뿐만 아니라 모의실험에서 제 1종 오류가 정해진 유의수준에 가까운 것을 확인하였고, 검정적이 더 높음을 볼 수 있었다.

Linear regression method, proposed by Haseman and Elston(1972), for detecting linkage to a quantitative trait of sib pairs is a linkage testing method for a single locus and a single trait. However, multivariate methods for detecting linkage are needed, when information from each of several traits that are affected by the same major gene are available on each individual. Amos et al. (1990) extended the regression method of Haseman and Elston(1972) to incorporate observations of two or more traits by estimating the principal component linear function that results in the strongest correlation between the squared pair differences in the trait measurements and identity by descent at a marker locus. But, it is impossible to control the probability of type I errors with this method at present, since the exact distribution of the statistic that they use is yet unknown. In this paper, we propose a multivariate nonparametric trend test for detecting linkage to multiple traits. We compared with a simulation study the efficiencies of multivariate nonparametric trend test with those of the method developed by Amos et al. (1990) for quantitative traits data. For multivariate nonparametric trend test, the results of the simulation study reveal that the Type I error rates are close to the predetermined significance levels, and have in general high powers.

키워드

참고문헌

  1. Amos, C. I., Elston, R. C., Bonney, G. E., Keats, B. J. B and Berenson, G. S. (1990). A multivariate method for detecting genetic linkage, with application to a pedigree with an adverse lipoprotein phenotype, The American Journal of Human Genetics, 47, 247-254
  2. Anderson, T. W. (1984). An Introduction to Multivariate Statistical Analysis, 2nd ed., John Wiley & Sons, New York
  3. Bae, Y., Park, C., Han, J., Hong, Y. J., Song, H. H., Shin, E. S., Lee, J. E., Han, B. G., Jang, Y., Shin, D. J. and Yoon, S. K. (2007). Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans, Journal of Human Hypertension, 21, 159-166 https://doi.org/10.1038/sj.jhh.1002110
  4. Dietz, E. J. (1989). Multivariate generalizations of Jonckheere's test for ordered alternatives, Communications in Statistics: Theory and Methods, 18, 3763-3783 https://doi.org/10.1080/03610928908830122
  5. Elston, R. C., Buxbaum, S., Jacobs, K. B. and Olson, J. M. (2000). Haseman and Elston revisited, Genetic Epidemiology, 19, 1-17 https://doi.org/10.1002/1098-2272(200007)19:1<1::AID-GEPI1>3.0.CO;2-E
  6. Falconer, D. S. and Mackay, T. F. C. (1996). Introduction to Quantitative Genetics, 4th ed., Longman Scientific & Technical, New York
  7. Gibbons, J. D. (1985). Nonparametric Statistical Inference, 2nd ed., Marcel Dekker, New York
  8. Haseman, J. K. and Elston, R. C. (1972). The investigation of linkage between a quantitative trait and a marker locus, Behavior Genetics, 2, 3-19 https://doi.org/10.1007/BF01066731
  9. 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
  10. Kim, M. K., Hong, Y. J. and Song, H. H. (2006). Nonparametric trend statistic incorporating dispersion diffrerences in sib pair linkage for quantitative traits, Human Heredity, 62, 1-11 https://doi.org/10.1159/000095597
  11. Lehmann, E. L. (1975). Nonparametrics: Statistical Methods Based on Ranks, Holden-Day, San Francisco
  12. Mann, H. B. and Whitney, D. R. (1947). On a test of whether one of two random variables is stochastically larger than the other, The Annals of Mathematical Statistics, 18, 50-60 https://doi.org/10.1214/aoms/1177730491
  13. Seber, G. A. F. (1988). Multivariate Observations, John Wiley & Sons, New York
  14. Siegel, S. and Tukey, J. W. (1960). A nonparametric sum of ranks procedure for relative spread in unpaired samples, Journal of the American Statistical Association, 55, 429-445 https://doi.org/10.2307/2281906
  15. 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
  16. Tryon, P. V. and Hettmansperger, T. P. (1973). A class of non-parametric tests for homogeneity against ordered alternatives, The Annals of Statistics, 1, 1061-1070 https://doi.org/10.1214/aos/1176342557
  17. Wan, Y., Cohen, J. and Guerra, R. (1997). A permutation test for the robust sib-pair linkage method, Annals of Human Genetics, 61, 79-87
  18. Wang, J., Guerra, R. and Cohen, J. (1998). Statistically robust approaches for sib-pairlinkage analysis, Annals of Human Genetics, 62, 349-359 https://doi.org/10.1046/j.1469-1809.1998.6240349.x
  19. Wagener, D., Kuller, L., Orchard, T., LaPorte, R., Rabin, B. and Drash, A. (1982). Pittsburgh diabetes mellitus study. II. Secondary attack rates in Families with insulin-dependent diabetes mellitus, American Journal of Epidemiology, 115, 868-878 https://doi.org/10.1093/oxfordjournals.aje.a113374