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Improved estimation of SNP heritability using Bayesian multiple-phenotype models

机译:使用贝叶斯多表型模型改进的SNP遗传力估计

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摘要

Linear mixed models (LMM) are widely used to estimate narrow sense heritability explained by tagged single-nucleotide polymorphisms (SNPs). However, those estimates are valid only if large sample sizes are used. We propose a Bayesian covariance component model (BCCM) that takes into account the genetic correlation among phenotypes and genetic correlation among individuals. The use of the BCCM allows us to circumvent issues related to small sample sizes, including overfitting and boundary estimates. Using expression of genes in breast cancer pathway, obtained from the Multiple Tissue Human Expression Resource (MuTHER) project, we demonstrate a significant improvement in the accuracy of SNP-based heritability estimates over univariate and likelihood-based methods. According to the BCCM, except CHURC1 (h2 = 0.27, credible interval = (0.2, 0.36)), all tested genes have trivial heritability estimates, thus explaining why recent progress in their eQTL identification has been limited.
机译:线性混合模型(LMM)被广泛用于估计由标记的单核苷酸多态性(SNP)解释的狭义遗传力。但是,这些估计仅在使用大样本量的情况下才有效。我们提出了一种贝叶斯协方差成分模型(BCCM),该模型考虑了表型之间的遗传相关性和个体之间的遗传相关性。 BCCM的使用使我们能够规避与小样本量有关的问题,包括过度拟合和边界估计。使用从多组织人类表达资源(MuTHER)项目获得的乳腺癌途径中的基因表达,我们证明了与单变量和基于可能性的方法相比,基于SNP的遗传力估计值的准确性有了显着提高。根据BCCM,除了CHURC1(h 2 = 0.27,可信区间=(0.2,0.36))之外,所有测试的基因均具有微弱的遗传力估计值,从而解释了为何最近对其eQTL鉴定的研究受到限制。

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