The Korean Journal of Applied Statistics (응용통계연구)

The Korean Statistical Society (한국통계학회)
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Comparison of Methods for Linkage Analysis of Affected Sibship Data

이환 형제 자료에 대한 유전적 연관성 분석 방법의 비교

  • Go, Min-Jin (Department of Biostatistics, Yonsei University) ;
  • Lim, Kil-Seob (Department of Biostatistics, Yonsei University) ;
  • Lee, Hak-Bae (Department of Applied Statistics, Yonsei University) ;
  • Song, Ki-Jun (Department of Biostatistics, Yonsei University)
  • 고민진 (연세대학교 의학통계학과) ;
  • 임길섭 (연세대학교 의학통계학과) ;
  • 이학배 (연세대학교 응용통계학과) ;
  • 송기준 (연세대학교 의학통계학과)
  • Published : 2009.04.30
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Abstract

For complex diseases such as diabetes, hypertension, it is believed that model-free methods might work better because they do not require a precise knowledge of the mode of inheritance controlling the disease trait. This is done by estimating the sharing probabilities that a pair shares zero, one, or two alleles identical by descent(IBD) and has some specific branches of test procedure, i.e., the mean test, the proportion test, and the minmax test. Among them, the minmax test is known to be more robust than others regardless of genetic mode of inheritance in current use. In this study, we compared the power of the methods which are based on minmax test and considering weighting schemes for sib-pairs to analyze sibship data. In simulation result, we found that the method based on Suarez' was more powerful than any others without respect to marker allele frequency, genetic mode of inheritance, sibship size. Also, The power of both Suarez- and Hodge-based methods was higher when marker allele frequency and sibship size were higher, and this result was remarkable in dominant mode of inheritance especially.

질적 형질에 대한 유전적 연관성 분석은 크게 두 가지로 구분 할 수 있는데, 모형 기반분석과 그렇지 않은 모형 무관 분석 방법이다. 복합질병의 경우 멘델의 유전법칙을 잘 따르지 않기 때문에 모형 기반 분석 방법을 사용하는 것보다 모형 무관 분석 방법을 사용하는 것이 효율적이라고 알려져 있다. 이러한 모형 무관 분석 방법 중 이환 형제 쌍 자료를 이용한 분석 방법은 형제 쌍 간의 유전적 일치 비율을 기준으로 공유하고 있는 대립유전자의 분포를 이용하는 것으로 크게 proportion test, mean test, minmax test로 구분 할 수 있다. 본 연구에서는 형제집단자료로 확장된 경우, 유전 형식에 상관없이 로버스트한 방법으로 알려진 minmax test에 형제 쌍의 가중치를 고려할 수 있는 방법들 즉, 동일 가중 방법, Suarez의 방법, Hodge의 방법, Sham 등의 방법을 적용하여 그 성능을 비교하였다. 모의실험 자료를 이용하여 비교한 결과 표식유전자의 빈도, 형질의 유전 형식, 형제수에 상관없이 Suarez의 방법이 가장 검정력이 높은 방법으로 드러났다. 또한, 동일 가중 방법을 제외하고는 표식유전자의 빈도가 높아질수록, 형제수가 많아질수록 더 높은 검정력을 보였고, 이러한 현상은 우성 유전 형식을 가정한 자료에서 더욱 두드러지게 나타났다.

Keywords

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