Estimating heritability of complex traits from genome-wide association studies using IBS-based Haseman-Elston regression.
Estimating heritability of complex traits from genome-wide association studies using IBS-based Haseman-Elston regression.
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DOI：
10.3389/fgene.2014.00107
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发表时间：
2014
影响因子：
3.7
通讯作者：
Chen GB
中科院分区：
文献类型：
--
作者：
Chen GB
探索复杂性状的遗传力是统计遗传学的中心焦点。在以往提出的各种遗传力估计方法中，方差分量法在利用标记估计遗传力时具有优势。由于从全基因组关联研究获得的数据的高维性质，其中遗传结构通常是未知的，所以最合适的遗传力估计模型通常是不清楚的。Haseman-Elston(HE)回归是一种最初仅用于连锁研究的方差分量方法。然而，这项研究为改进的HE模型提供了理论基础，该模型为数量性状的连锁不平衡建模，因此可以用于GWAS。在用州同一性(IBS)分数替换相同(IBD)分数后，我们将基于IBS的HE回归应用于单标记关联研究(场景I)，并使用多个标记估计方差分量(场景II)。在情景II中，我们讨论了HE回归和混合线性模型等价的情况；当加性方差存在协方差分量时，观察这两种方法之间的差异。当我们在随后的模拟研究中将基于IBS的HE回归扩展到病例对照研究时，我们发现它提供了对遗传度的几乎无偏的估计，比通过混合线性模型估计的更精确。因此，对于病例对照方案，HE回归更可取。遗传分析资料库(GEAR；http://sourceforge.net/p/gbchen/wiki/GEAR/)软件实现了HE回归方法，并可免费获得。
Exploring heritability of complex traits is a central focus of statistical genetics. Among various previously proposed methods to estimate heritability, variance component methods are advantageous when estimating heritability using markers. Due to the high-dimensional nature of data obtained from genome-wide association studies (GWAS) in which genetic architecture is often unknown, the most appropriate heritability estimator model is often unclear. The Haseman–Elston (HE) regression is a variance component method that was initially only proposed for linkage studies. However, this study presents a theoretical basis for a modified HE that models linkage disequilibrium for a quantitative trait, and consequently can be used for GWAS. After replacing identical by descent (IBD) scores with identity by state (IBS) scores, we applied the IBS-based HE regression to single-marker association studies (scenario I) and estimated the variance component using multiple markers (scenario II). In scenario II, we discuss the circumstances in which the HE regression and the mixed linear model are equivalent; the disparity between these two methods is observed when a covariance component exists for the additive variance. When we extended the IBS-based HE regression to case-control studies in a subsequent simulation study, we found that it provided a nearly unbiased estimate of heritability, more precise than that estimated via the mixed linear model. Thus, for the case-control scenario, the HE regression is preferable. GEnetic Analysis Repository (GEAR; http://sourceforge.net/p/gbchen/wiki/GEAR/) software implemented the HE regression method and is freely available.
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