School of Mathematics and Statistics, University of Sheffield, Sheffield, UK.
Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield Medical School, Sheffield, UK.
Genet Epidemiol. 2021 Jun;45(4):386-401. doi: 10.1002/gepi.22375. Epub 2021 Jan 6.
The Gaussian distribution is usually the default causal single-nucleotide polymorphism (SNP) effect size prior in Bayesian population-based fine-mapping association studies, but a recent study showed that the heavier-tailed Laplace prior distribution provided a better fit to breast cancer top hits identified in genome-wide association studies. We investigate the utility of the Laplace prior as an effect size prior in univariate fine-mapping studies. We consider ranking SNPs using Bayes factors and other summaries of the effect size posterior distribution, the effect of prior choice on credible set size based on the posterior probability of causality, and on the noteworthiness of SNPs in univariate analyses. Across a wide range of fine-mapping scenarios the Laplace prior generally leads to larger 90% credible sets than the Gaussian prior. These larger credible sets for the Laplace prior are due to relatively high prior mass around zero which can yield many noncausal SNPs with relatively large Bayes factors. If using conventional credible sets, the Gaussian prior generally yields a better trade off between including the causal SNP with high probability and keeping the set size reasonable. Interestingly when using the less well utilised measure of noteworthiness, the Laplace prior performs well, leading to causal SNPs being declared noteworthy with high probability, whilst generally declaring fewer than 5% of noncausal SNPs as being noteworthy. In contrast, the Gaussian prior leads to the causal SNP being declared noteworthy with very low probability.
在基于人群的贝叶斯精细定位关联研究中,高斯分布通常是默认的因果单核苷酸多态性 (SNP) 效应大小先验分布,但最近的一项研究表明,重尾的拉普拉斯先验分布更适合全基因组关联研究中确定的乳腺癌顶级命中。我们研究了拉普拉斯先验作为单变量精细定位研究中效应大小先验的效用。我们考虑使用贝叶斯因子和其他效应大小后验分布的摘要来对 SNP 进行排序,先验选择对基于因果概率的可信集大小的影响,以及对单变量分析中 SNP 的显著性的影响。在广泛的精细映射场景中,拉普拉斯先验通常会导致比高斯先验更大的 90%可信集。拉普拉斯先验的这些更大的可信集是由于零周围的先验质量相对较高,这可能导致许多具有相对较大贝叶斯因子的非因果 SNP。如果使用传统的可信集,高斯先验通常可以在高概率包含因果 SNP 与保持集合大小合理之间取得较好的权衡。有趣的是,当使用不太常用的显著性度量时,拉普拉斯先验表现良好,导致因果 SNP 以高概率被宣布为显著,而通常将少于 5%的非因果 SNP 宣布为显著。相比之下,高斯先验导致因果 SNP 被宣布为显著的概率非常低。