Journal of Preventive Medicine and Public Health

  • 제37권4호
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  • Pages.366-372
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  • 2004
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  • 1975-8375(pISSN)
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  • 2233-4521(eISSN)
대한예방의학회 (The Korean Society for Preventive Medicine)
권호 표지

일배체형에 기초한 연쇄분석의 통계학적 알고리즘 연구

Statistical Algorithm in Genetic Linkage Based on Haplotypes

  • 김진흠 (수원대학교 통계정보학과) ;
  • 강대룡 (연세대학교 의과대학 예방의학교실) ;
  • 이윤경 (연세대학교 대학원 보건학과) ;
  • 신선미 (연세대학교 대학원 보건학과) ;
  • 서일 (연세대학교 의과대학 예방의학교실) ;
  • 남정모 (연세대학교 의과대학 예방의학교실)
  • Kim, Jin-Heum (Department of Applied Statistics, University of Suwon) ;
  • Kang, Dae-Ryong (Department of Preventive Medicine and Public Health, Yonsei University College of Medicine) ;
  • Lee, Yun-Kyung (Graduate School of Public Health, Yonsei University) ;
  • Shin, Sun-Mi (Graduate School of Public Health, Yonsei University) ;
  • Suh, Il (Department of Preventive Medicine and Public Health, Yonsei University College of Medicine) ;
  • Nam, Chung-Mo (Department of Preventive Medicine and Public Health, Yonsei University College of Medicine)
  • 발행 : 2004.12.01
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초록

Objectives : This study was conducted to propose a new transmission/disequilibrium test(TDT) to test the linkage between genetic markers and disease-susceptibility genes based on haplotypes. Simulation studies were performed to compare the proposed method with that of Zhao et al. in terms of type I error probability and powers. Methods : We estimated the haplotype frequencies using the expectation-maximization(EM) algorithm with parents genotypes taken from a trio dataset, and then constructed a two-way contingency table containing estimated frequencies to all possible pairs of parents haplotypes. We proposed a score test based on differences between column marginals and their corresponding row marginals. The test also involved a covariance structure of marginal differences and their variances. In simulation, we considered a coalescent model with three genetic markers of biallele to investigate the performance of the proposed test under six different configurations. Results : The haplotype-based TDT statistics, our test and Zhao et al.'s test satisfied a type I error probability, but the TDT test based on single locus showed a conservative trend. As expected, the tests based on haplotypes also had better powers than those based on single locus. Our test and that of Zhao et al. were comparable in powers. Conclusion : We proposed a TDT statistic based on haplotypes and showed through simulations that our test was more powerful than the single locus-based test. We will extend our method to multiplex data with affected and/or unaffected sibling(s) or simplex data having only one parent s genotype.

키워드

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