从 SNP 数据中检测和量化复杂性状的近交衰退。
Detection and quantification of inbreeding depression for complex traits from SNP data.
机构信息
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
出版信息
Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8602-8607. doi: 10.1073/pnas.1621096114. Epub 2017 Jul 26.
Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in [Formula: see text] participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between -2.3 and -5.2 phenotypic SDs for complete inbreeding; [Formula: see text]). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.
量化近交的影响对于描述复杂性状的遗传结构至关重要。本研究通过理论和模拟突出了三种常用的基于 SNP 的近交度量方法的优缺点，这些方法常用于估计近交衰退（ID）。我们证明了因果变异和 SNP 之间的连锁不平衡（LD）异质性会导致 ID 估计的偏差，并且我们开发了一种使用 LD 和次要等位基因频率分层推断（LDMS）来纠正这种偏差的方法。我们使用 LDMS 对英国生物库中 25 项特征进行了 ID 量化，并确认了 4 项特征的先前公布的 ID。我们发现了握力、腰围/臀围比以及视觉和听觉敏锐度的独特 ID 证据（完全近交的 ID 介于 -2.3 到 -5.2 个表型 SD 之间；[Formula: see text]）。我们的结果表明，仔细选择近交度量方法并结合 LDMS 分层，可以提高 SNP 数据中 ID 的检测和量化。
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