Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals

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• 作者：Juan Pablo Lewinger (1)
  Sophia SF Lee (1) (2)
  Joanna Biernacka (1) (2)
  Long Yang Wu (1)
  Haijiang Steven Shi (1)
  Shelley B Bull (1) (2)
  
• 刊名：BMC Genetics
• 出版年：2005
• 出版时间：December 2005
• 年：2005
• 卷：6
• 期：1-supp
• 全文大小：491KB
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• 作者单位：Juan Pablo Lewinger (1)
  Sophia SF Lee (1) (2)
  Joanna Biernacka (1) (2)
  Long Yang Wu (1)
  Haijiang Steven Shi (1)
  Shelley B Bull (1) (2)
  
  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5
  2. Department of Public Health Sciences, University of Toronto, 12 Queen's Park Crescent West, Toronto, Ontario, Canada, M5S 1A8
  

文摘

We use the Genetic Analysis Workshop 14 simulated data to explore the effectiveness of a two-stage strategy for mapping complex disease loci consisting of an initial genome scan with confidence interval construction for gene location, followed by fine mapping with family-based tests of association on a dense set of single-nucleotide polymorphisms. We considered four types of intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval based on the position of the maximum Zlr score, and asymptotic and bootstrap confidence intervals based on a generalized estimating equations method. For fine mapping we considered two family-based tests of association: a test based on a likelihood ratio statistic and a transmission-disequilibrium-type test implemented in the software FBAT. In two of the simulation replicates, we found that the bootstrap confidence intervals based on the peak Zlr and the 1-LOD support interval always contained the true disease loci and that the likelihood ratio test provided further strong confirmatory evidence of the presence of disease loci in these regions.