School of Computing and Information Systems, The University of Melbourne, Parkville, 3010, Australia.
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, 3010, Australia.
Brief Bioinform. 2021 Sep 2;22(5). doi: 10.1093/bib/bbab093.
The high accuracy of recent haplotype phasing tools is enabling the integration of haplotype (or phase) information more widely in genetic investigations. One such possibility is phase-aware expression quantitative trait loci (eQTL) analysis, where haplotype-based analysis has the potential to detect associations that may otherwise be missed by standard SNP-based approaches.
We present eQTLHap, a novel method to investigate associations between gene expression and genetic variants, considering their haplotypic and genotypic effect. Using multiple simulations based on real data, we demonstrate that phase-aware eQTL analysis significantly outperforms typical SNP-based methods when the causal genetic architecture involves multiple SNPs. We show that phase-aware eQTL analysis is robust to phasing errors, showing only a minor impact ($<4%$) on sensitivity. Applying eQTLHap to real GEUVADIS and GTEx datasets detects numerous novel eQTLs undetected by a single-SNP approach, with 22 eQTLs replicating across studies or tissue types, highlighting the utility of phase-aware eQTL analysis.
https://github.com/ziadbkh/eQTLHap.
Supplementary data are available at Briefings in Bioinformatics online.
最近的单倍型定相工具的高精度使得单倍型（或相位）信息能够更广泛地整合到遗传研究中。一种这样的可能性是具有相位意识的表达数量性状基因座（eQTL）分析，其中基于单倍型的分析有可能检测到可能被标准 SNP 方法遗漏的关联。
我们提出了 eQTLHap，这是一种新的方法，用于研究基因表达与遗传变异之间的关联，同时考虑它们的单倍型和基因型效应。使用基于真实数据的多种模拟，我们证明了当因果遗传结构涉及多个 SNP 时，具有相位意识的 eQTL 分析明显优于典型的 SNP 方法。我们表明，相位感知的 eQTL 分析对定相错误具有鲁棒性，仅对灵敏度产生轻微影响（<4%）。将 eQTLHap 应用于真实的 GEUVADIS 和 GTEx 数据集，检测到许多 SNP 方法无法检测到的新 eQTL，其中 22 个 eQTL 在不同研究或组织类型中具有复制性，突出了相位感知的 eQTL 分析的实用性。
https://github.com/ziadbkh/eQTLHap。
补充数据可在Briefings in Bioinformatics 在线获取。
