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SNP-based linkage analysis in extended pedigrees: Comparison between two alternative approaches

机译：扩展谱系中基于SNP的连锁分析：两种替代方法之间的比较

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Background: Linkage analysis on extended pedigrees is often challenged by the high computational demand of exact identity-by-descent (IBD) matrix reconstruction. When such an analysis becomes not feasible, two alternative solutions are contrasted: a full pedigree analysis based on approximate IBD estimation versus a pedigree splitting followed by exact IBD estimation. A multiple splitting (MS) approach, which combines linkage results across different splitting configurations, has been proposed to increase the power of single-split solutions. Methods: To assess whether MS can achieve a comparable power to a full pedigree analysis, we compared the power of linkage on a very large pedigree in both simulated and real-case scenarios, using variance components linkage analysis of a dense SNP array. Results: Our results confirm that the power to detect linkage is affected by the pedigree size. The MS approach showed higher power than the single-split analysis, but it was substantially less powerful than the full pedigree approach in both scenarios, at any level of significance and variance explained by a quantitative trait locus. Conclusion: The MS approach should always be preferred to analyses based on a single split but, when adequate computational resources are available, a full pedigree analysis is better than the MS analysis. Rather than focusing on how to best split a pedigree, it might be more valuable to identify computational solutions that can make the IBD estimation of dense-marker maps practically feasible, thus allowing a full pedigree analysis.
机译：背景：对扩展谱系的链接分析经常受到精确的后代身份识别（IBD）矩阵重构的高计算需求的挑战。当这样的分析变得不可行时，将对两个备选解决方案进行对比：基于近似IBD估计的完整谱系分析与基于谱系划分的精确IBD估计。提出了一种将不同拆分配置之间的链接结果组合在一起的多重拆分（MS）方法，以提高单拆分解决方案的功能。方法：为了评估MS是否可以达到与完整谱系分析相当的功效，我们使用密集SNP数组的方差分量链接分析，在模拟和真实情况下比较了非常大谱系的链接功效。结果：我们的结果证实了检测连锁的能力受谱系大小的影响。 MS方法显示出比单分裂分析更高的功效，但是在两种情况下，无论通过显着性状基因位点解释的显着性和方差水平如何，MS方法都比全谱系方法强大得多。结论：MS方法应始终首选于基于单个拆分的分析，但是，当有足够的计算资源可用时，完整的谱系分析比MS分析更好。与其专注于如何最佳地分割血统书，不如找出可以使IBD估计密集标记图可行的计算解决方案更有价值，从而进行完整的血统书分析。

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