Dietter Johannes, Spiegel Alexander, an Mey Dieter, Pflug Hans-Joachim, Al-Kateb Hussam, Hoffmann Katrin, Wienker Thomas F, Strauch Konstantin
Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Eur J Hum Genet. 2004 Jul;12(7):542-50. doi: 10.1038/sj.ejhg.5201196.
We have optimized and parallelized the GENEHUNTER-TWOLOCUS program that allows to perform linkage analysis with two trait loci in the multimarker context. The optimization of the serial program, before parallelization, results in a speedup of a factor of more than 10. The parallelization affects the two-locus-score calculation, which is predominant in terms of computation time. We obtain perfect speedup, that is, the computation time decreases exactly by a factor of the number of processors. In addition, two-locus LOD and NPL scores are now calculated for varying genetic positions of both disease loci, not just one locus varied and the position of the other disease locus fixed, as before. This results in easily interpretable 3-D plots. We have reanalyzed a pedigree with hypercholesterolemia using our new version of GENEHUNTER-TWOLOCUS. Whereas originally, two individuals had to be discarded due to excessive computation-time demands, the entire 17-bit pedigree could now be analyzed as a whole. We obtain a two-trait-locus LOD score of 5.49 under a multiplicative model, compared to LOD scores of 3.08 and 2.87 under a heterogeneity and additive model, respectively. This further increases evidence for linkage to both 1p36.1-p35 and 13q22-q32 regions, and corroborates the hypothesis that the two genes act in a multiplicative way on LDL cholesterol level. Furthermore, we compare the computation times for two-trait-locus analysis needed by the programs GENEHUNTER-TWOLOCUS, TLINKAGE, and SUPERLINK. Altogether, our algorithmic improvements of GENEHUNTER-TWOLOCUS allow researchers to analyze complex diseases under realistic two-trait-locus models with pedigrees of reasonable size and using many markers.
我们已经对GENEHUNTER-TWOLOCUS程序进行了优化和并行化处理，该程序能够在多标记背景下对两个性状位点进行连锁分析。在并行化之前，对串行程序的优化使速度提高了10倍以上。并行化影响两位点得分计算，而该计算在计算时间方面占主导地位。我们实现了完美加速，也就是说，计算时间恰好减少了处理器数量的倍数。此外，现在针对两个疾病位点的不同基因位置计算两位点LOD和NPL得分，而不像以前那样仅改变一个位点的位置并固定另一个疾病位点的位置。这产生了易于解释的三维图。我们使用新版的GENEHUNTER-TWOLOCUS重新分析了一个患有高胆固醇血症的家系。原本由于计算时间需求过大，有两个个体不得不被舍弃，而现在整个17代家系都可以作为一个整体进行分析。在乘法模型下，我们得到的双性状位点LOD得分为5.49，而异质性模型和加法模型下的LOD得分分别为3.08和2.87。这进一步增加了与1p36.1 - p35和13q22 - q32区域连锁的证据，并证实了这两个基因以乘法方式作用于低密度脂蛋白胆固醇水平的假设。此外，我们比较了GENEHUNTER-TWOLOCUS、TLINKAGE和SUPERLINK程序进行双性状位点分析所需的计算时间。总之，我们对GENEHUNTER-TWOLOCUS的算法改进使研究人员能够在现实的双性状位点模型下，使用合理规模的家系并结合许多标记来分析复杂疾病。
