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CAUSALdb:一个数据库,用于通过全基因组关联研究的汇总统计数据来识别疾病/特征因果变异。

CAUSALdb: a database for disease/trait causal variants identified using summary statistics of genome-wide association studies.

机构信息

2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

出版信息

Nucleic Acids Res. 2020 Jan 8;48(D1):D807-D816. doi: 10.1093/nar/gkz1026.


DOI:10.1093/nar/gkz1026
PMID:31691819
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7145620/
Abstract

Genome-wide association studies (GWASs) have revolutionized the field of complex trait genetics over the past decade, yet for most of the significant genotype-phenotype associations the true causal variants remain unknown. Identifying and interpreting how causal genetic variants confer disease susceptibility is still a big challenge. Herein we introduce a new database, CAUSALdb, to integrate the most comprehensive GWAS summary statistics to date and identify credible sets of potential causal variants using uniformly processed fine-mapping. The database has six major features: it (i) curates 3052 high-quality, fine-mappable GWAS summary statistics across five human super-populations and 2629 unique traits; (ii) estimates causal probabilities of all genetic variants in GWAS significant loci using three state-of-the-art fine-mapping tools; (iii) maps the reported traits to a powerful ontology MeSH, making it simple for users to browse studies on the trait tree; (iv) incorporates highly interactive Manhattan and LocusZoom-like plots to allow visualization of credible sets in a single web page more efficiently; (v) enables online comparison of causal relations on variant-, gene- and trait-levels among studies with different sample sizes or populations and (vi) offers comprehensive variant annotations by integrating massive base-wise and allele-specific functional annotations. CAUSALdb is freely available at http://mulinlab.org/causaldb.

摘要

全基因组关联研究(GWAS)在过去十年中彻底改变了复杂性状遗传学领域,但对于大多数重要的基因型-表型关联,真正的因果变异仍然未知。确定和解释因果遗传变异如何赋予疾病易感性仍然是一个巨大的挑战。在此,我们引入了一个新的数据库 CAUSALdb,以整合迄今为止最全面的 GWAS 汇总统计数据,并使用统一处理的精细映射来识别可信的潜在因果变异集。该数据库具有六个主要特点:(i)整理了五个超级人类群体和 2629 个独特特征的 3052 个高质量、可精细映射的 GWAS 汇总统计数据;(ii)使用三种最先进的精细映射工具估计 GWAS 显著位点中所有遗传变异的因果概率;(iii)将报告的特征映射到强大的本体 MeSH,使用户可以轻松在特征树上浏览研究;(iv)整合了高度交互的曼哈顿和类似 LocusZoom 的图,以便更有效地在单个网页上可视化可信集;(v)通过整合大量基于碱基和等位基因特异性的功能注释,实现了在不同样本量或人群的研究之间在线比较变异、基因和特征水平上的因果关系;(vi)提供了全面的变异注释,通过整合大量基于碱基和等位基因特异性的功能注释。CAUSALdb 可在 http://mulinlab.org/causaldb 免费获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/89ac0d7b539d/gkz1026fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/b133ee53a28a/gkz1026fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/3f12dbd21b68/gkz1026fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/89ac0d7b539d/gkz1026fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/b133ee53a28a/gkz1026fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/3f12dbd21b68/gkz1026fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c0e/7145620/89ac0d7b539d/gkz1026fig3.jpg

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本文引用的文献

[1]
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Nucleic Acids Res. 2019-12-2

[2]
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Nat Genet. 2019-8-19

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Nat Rev Genet. 2019-8

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Nucleic Acids Res. 2019-1-8

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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.

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