Huang B E, Amos C I, Lin D Y
Department of Biostatistics, University of North Carolina, North Carolina 27599-7420, USA.
Genet Epidemiol. 2007 Dec;31(8):803-12. doi: 10.1002/gepi.20242.
The analysis of genomewide association studies requires methods that are both computationally feasible and statistically powerful. Given the large-scale collection of single nucleotide polymorphisms (SNPs), it is desirable to explore the information contained in their interrelationships. In particular, utilizing haplotypes rather than individual SNPs and accounting for correlations of polymorphisms in adjustment for multiple testing can lead to increased power. We present a statistically powerful and numerically efficient method based on sliding windows of adjacent SNPs to detect haplotype-disease association in genomewide studies. This method consists of an efficient algorithm to calculate a proper likelihood-ratio statistic for any given window of SNPs, along with an accurate and efficient Monte Carlo procedure to adjust for multiple testing. Simulation studies using the HapMap data showed that the proposed method performs well in realistic situations. We applied the new method to a case-control study on rheumatoid arthritis and identified several loci worthy of further investigations.
全基因组关联研究的分析需要计算上可行且统计效力强大的方法。鉴于单核苷酸多态性(SNP)的大规模收集,探索其相互关系中包含的信息是很有必要的。特别是,利用单倍型而非单个SNP,并在多重检验校正中考虑多态性的相关性,可提高检验效能。我们提出了一种基于相邻SNP滑动窗口的统计效力强大且数值高效的方法,用于在全基因组研究中检测单倍型与疾病的关联。该方法包括一个高效算法,用于为任何给定的SNP窗口计算适当的似然比统计量,以及一个准确高效的蒙特卡罗程序,用于校正多重检验。使用HapMap数据进行的模拟研究表明,所提出的方法在实际情况下表现良好。我们将新方法应用于一项类风湿性关节炎的病例对照研究,并确定了几个值得进一步研究的基因座。