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使用 FUMA 进行遗传关联的功能映射和注释。

Functional mapping and annotation of genetic associations with FUMA.

机构信息

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, 1081 HV, The Netherlands.

VU University Medical Center (VUMC), Alzheimercentrum, Amsterdam, 1081 HV, The Netherlands.

出版信息

Nat Commun. 2017 Nov 28;8(1):1826. doi: 10.1038/s41467-017-01261-5.


DOI:10.1038/s41467-017-01261-5
PMID:29184056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5705698/
Abstract

A main challenge in genome-wide association studies (GWAS) is to pinpoint possible causal variants. Results from GWAS typically do not directly translate into causal variants because the majority of hits are in non-coding or intergenic regions, and the presence of linkage disequilibrium leads to effects being statistically spread out across multiple variants. Post-GWAS annotation facilitates the selection of most likely causal variant(s). Multiple resources are available for post-GWAS annotation, yet these can be time consuming and do not provide integrated visual aids for data interpretation. We, therefore, develop FUMA: an integrative web-based platform using information from multiple biological resources to facilitate functional annotation of GWAS results, gene prioritization and interactive visualization. FUMA accommodates positional, expression quantitative trait loci (eQTL) and chromatin interaction mappings, and provides gene-based, pathway and tissue enrichment results. FUMA results directly aid in generating hypotheses that are testable in functional experiments aimed at proving causal relations.

摘要

全基因组关联研究(GWAS)的主要挑战之一是精确定位可能的因果变异。GWAS 的结果通常不能直接转化为因果变异,因为大多数命中的变异都在非编码区或基因间区,而连锁不平衡的存在导致效应在多个变异体上呈统计学上的分散。GWAS 后注释有助于选择最有可能的因果变异(多个)。有多种资源可用于 GWAS 后注释,但这些可能很耗时,并且不能为数据解释提供集成的可视化辅助工具。因此,我们开发了 FUMA:一个基于网络的集成平台,使用来自多个生物资源的信息来促进 GWAS 结果的功能注释、基因优先级排序和交互式可视化。FUMA 可以容纳位置、表达数量性状基因座(eQTL)和染色质相互作用图谱,并提供基于基因、途径和组织的富集结果。FUMA 的结果直接有助于生成假设,这些假设可以在旨在证明因果关系的功能实验中进行测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/59f794ab5e7b/41467_2017_1261_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/a0bd2584b014/41467_2017_1261_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/28b37e67cb1a/41467_2017_1261_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/5296ea75892b/41467_2017_1261_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/59f794ab5e7b/41467_2017_1261_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/a0bd2584b014/41467_2017_1261_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/28b37e67cb1a/41467_2017_1261_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/5296ea75892b/41467_2017_1261_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/5705698/59f794ab5e7b/41467_2017_1261_Fig4_HTML.jpg

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[1]
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本文引用的文献

[1]
The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions.

Genome Biol. 2018-10-4

[2]
Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights.

Nat Genet. 2018-4-9

[3]
Identification of context-dependent expression quantitative trait loci in whole blood.

Nat Genet. 2016-12-5

[4]
Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

Cell. 2016-11-17

[5]
A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome.

Cell Rep. 2016-11-15

[6]
Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23.

Genome Biol. 2016-11-1

[7]
Translating genome-wide association findings into new therapeutics for psychiatry.

Nat Neurosci. 2016-10-26

[8]
Chromosome conformation elucidates regulatory relationships in developing human brain.

Nature. 2016-10-27

[9]
Analysis of protein-coding genetic variation in 60,706 humans.

Nature. 2016-8-18

[10]
The Ensembl Variant Effect Predictor.

Genome Biol. 2016-6-6

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