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Identifying Causal Variants by Fine Mapping Across Multiple Studies

机译:通过跨多个研究的精细映射识别因果变异

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Genome-Wide Association Studies (GWAS) have successfully identified numerous genetic variants associated with a variety of complex traits in humans. However, most of these associated variants are not causal, and are simply in Linkage Disequilibrium (LD) with the true causal variants. This problem is addressed by statistical "fine mapping" methods, which attempt to prioritize a small subset of variants for further testing while accounting for LD structure [1]. CAVIAR [2] introduced a widely-adopted Bayesian approach that accounted for uncertainty in association statistics using a multivariate normal (MVN) model and allowed for potentially multiple causal SNPs at a locus. There is growing interest in improving fine-mapping by leveraging information from multiple studies. One example of this is trans-ethnic fine mapping, which can significantly improve fine mapping power and resolution by leveraging the distinct LD structures in each population. However, existing methods either assume a single causal SNP at each locus or do not explicitly model heterogeneity, limiting their power.
机译:全基因组关联研究(GWAS)已成功鉴定出与人类多种复杂性状相关的众多遗传变异。但是,大多数这些相关的变体不是因果关系的,只是与真正的因果关系变体存在于连锁不平衡(LD)中。通过统计“精细映射”方法解决了该问题,该方法试图在考虑LD结构的同时优先考虑一小部分变体以进行进一步测试[1]。 CAVIAR [2]引入了一种广泛采用的贝叶斯方法,该方法使用多变量正态(MVN)模型解决了关联统计中的不确定性,并允许在某个位置潜在存在多个因果SNP。通过利用来自多个研究的信息来改善精细映射的兴趣日益浓厚。一个例子是跨种族精细映射,它可以通过利用每个群体中不同的LD结构来显着提高精细映射的能力和分辨率。但是,现有方法要么在每个位置假设单个因果SNP,要么未明确建模异质性,从而限制了它们的功能。

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