eQTL目录2023:新的数据集,X染色体QTL,以及转录水平QTL的改进检测和可视化。

IF 4.5 2区 生物学 Q1 Agricultural and Biological Sciences PLoS Genetics Pub Date : 2023-09-18 eCollection Date: 2023-09-01 DOI:10.1371/journal.pgen.1010932
Nurlan Kerimov, Ralf Tambets, James D Hayhurst, Ida Rahu, Peep Kolberg, Uku Raudvere, Ivan Kuzmin, Anshika Chowdhary, Andreas Vija, Hans J Teras, Masahiro Kanai, Jacob Ulirsch, Mina Ryten, John Hardy, Sebastian Guelfi, Daniah Trabzuni, Sarah Kim-Hellmuth, William Rayner, Hilary Finucane, Hedi Peterson, Abayomi Mosaku, Helen Parkinson, Kaur Alasoo
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引用次数: 1

摘要

eQTL目录是一个统一处理的人类分子数量性状基因座(QTL)的开放数据库。我们正在不断更新资源,以进一步提高其在解释与复杂性状的遗传关联方面的效用。在过去的两年里,我们将统一处理的研究数量从21项增加到31项,并为19项相容性研究添加了X染色体QTL。我们还实现了Leafcutter,以直接识别所有RNA测序数据集中剪接连接使用的QTL。最后,为了提高转录水平QTL的可解释性,我们开发了静态QTL覆盖图,该图显示了该区域所有170万个精细映射关联的基因型和平均RNA测序读数覆盖率之间的关联。为了说明这些更新对eQTL目录的效用,我们对英国生物库中的维生素D水平和eQTL编目中的所有分子QTL进行了共定位分析。尽管大多数GWAS基因座与eQTL和转录水平QTL共存,但我们发现,视觉检查有时可以用来区分初级剪接QTL和那些似乎是大效应基因表达QTL的次要结果的QTL。虽然这些视觉确认的初级剪接QTL仅解释了6/53的共定位信号,但它们的多效性明显低于eQTL,并在4/6例病例中确定了优先的因果基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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eQTL Catalogue 2023: New datasets, X chromosome QTLs, and improved detection and visualisation of transcript-level QTLs.

The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs). We are continuously updating the resource to further increase its utility for interpreting genetic associations with complex traits. Over the past two years, we have increased the number of uniformly processed studies from 21 to 31 and added X chromosome QTLs for 19 compatible studies. We have also implemented Leafcutter to directly identify splice-junction usage QTLs in all RNA sequencing datasets. Finally, to improve the interpretability of transcript-level QTLs, we have developed static QTL coverage plots that visualise the association between the genotype and average RNA sequencing read coverage in the region for all 1.7 million fine mapped associations. To illustrate the utility of these updates to the eQTL Catalogue, we performed colocalisation analysis between vitamin D levels in the UK Biobank and all molecular QTLs in the eQTL Catalogue. Although most GWAS loci colocalised both with eQTLs and transcript-level QTLs, we found that visual inspection could sometimes be used to distinguish primary splicing QTLs from those that appear to be secondary consequences of large-effect gene expression QTLs. While these visually confirmed primary splicing QTLs explain just 6/53 of the colocalising signals, they are significantly less pleiotropic than eQTLs and identify a prioritised causal gene in 4/6 cases.

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来源期刊
PLoS Genetics
PLoS Genetics 生物-遗传学
CiteScore
8.10
自引率
2.20%
发文量
438
审稿时长
1 months
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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