Genome-wide association (GWA) studies play a key role in current genetics research, unravelling genomic regions linked to phenotypic traits of interest in multiple species. Nevertheless, the extent of linkage disequilibrium (LD) may provide confounding results when significant genetic markers span along several contiguous cM. In this study, we have adapted the composite interval mapping approach to the GWA framework (composite GWA), in order to evaluate the impact of including competing (possibly linked) genetic markers when testing for the additive allelic effect inherent to a given genetic marker. We tested model performance on simulated data sets under different scenarios (i.e., qualitative trait loci effects, LD between genetic markers and width of the genomic region involved in the analysis). Our results showed that the genomic region had a small impact on the number of competing single nucleotide polymorphisms (SNPs) as well as on the precision of the composite GWA analysis. A similar conclusion was derived from the preferable range of LD between the tested SNP and competing SNPs, although moderate-to-high LD seemed to attenuate the loss of statistical power. The composite GWA improved specificity and reduced the number of significant genetic markers. The composite GWA model contributes a novel point of view for GWA analyses where testing circumscribed to the genomic region flanking each SNP (delimited by the nearest competing SNPs) and conditioning on linked markers increases the precision to locate causal mutations, but possibly at the expense of power.

中文翻译：

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通过复合全基因组关联分析进行精细定位。

全基因组关联（GWA）研究在当前的遗传学研究中发挥着关键作用，揭示了与多个物种感兴趣的表型性状相关的基因组区域。然而，当显着的遗传标记跨越几个连续的 cM 时，连锁不平衡 (LD) 的程度可能会提供令人困惑的结果。在本研究中，我们采用了 GWA 框架（复合 GWA）的复合区间作图方法，以便在测试给定遗传标记固有的加性等位基因效应时评估包括竞争（可能连锁）遗传标记的影响。我们在不同场景下的模拟数据集上测试了模型性能（即，定性性状位点效应、遗传标记之间的 LD 以及参与分析的基因组区域的宽度）。我们的结果表明，基因组区域对竞争性单核苷酸多态性 (SNP) 的数量以及复合 GWA 分析的精度影响很小。从测试的 SNP 和竞争 SNP 之间的 LD 最佳范围得出了类似的结论，尽管中到高 LD 似乎减弱了统计功效的损失。复合 GWA 提高了特异性并减少了重要遗传标记的数量。复合 GWA 模型为 GWA 分析提供了一种新颖的观点，其中测试限制在每个 SNP 侧翼的基因组区域（由最近的竞争 SNP 界定）并以连锁标记为条件，提高了定位因果突变的精度，但可能会牺牲力量。