Project description
The molecular basis of local gene co-expression and its impact on human disease
Genome-wide association studies (GWAS) have so far associated >10 000 genetic variants with disease and linked some of these disease variants to causal genes. Our understanding of a variant’s molecular link to disease is still a major challenge as most are found in the genome’s non-coding regions, act only in specific tissues and may affect several genes. Recent studies revealed that neighbouring genes are often co-expressed – they form co-expression domains (CODs) – and could be regulated by shared regulatory variants. The EU-funded CODer project aims to investigate how local gene co-expression is achieved and regulated by genetic variants and study their impact on human disease using cutting-edge datasets of single-cell RNA sequencing.
Objective
The genetic makeup intrinsic to each person shapes their particular traits, disease susceptibilities and treatment effectiveness, making understanding the functional impact of genetic variants one of the most pursued challenges in genetics research. Genome-wide association studies (GWAS) have so far associated >10,000 genetic variants with disease, with expression quantitative trait loci (eQTL) studies adamant in linking some of these disease variants to causal genes. Yet, understanding a variant’s molecular link to disease is still a major challenge, given that most are found in the genome’s non-coding regions, act only in specific tissues and may affect several genes. Recent studies revealed that neighbouring genes are often co-expressed – forming co-expression domains (CODs) – potentially regulated by shared regulatory variants, yet, this has been ignored in eQTL and GWAS studies. This project aims to investigate how local gene co-expression is achieved and regulated by genetic variants, and their impact on human disease. For this, I propose a novel genome-wide framework to detect human CODs and their regulatory variants (cod-QTLs) using transcriptomic profiles across hundreds of genotyped individuals. The mechanisms through which variants affect the expression of several genes will be discovered through causality inference and molecular characterisation using state-of-the-art datasets (e.g. Hi-C, promoter-enhancer maps). Notably, CODs’ tissue-specificity will be studied using gene expression across 53 human tissues and the co-expression variation across 120 individuals will be assessed using a cutting-edge dataset of single-cell RNA-seq. The impact of cod-QTLs on dozens of societal-relevant diseases will be determined by colocalization analysis with GWAS hits from the UK Biobank. This project promises to clarify fundamental aspects of gene (co-)regulation and provide functional interpretation of eQTLs and GWAS findings, including revealing novel disease genes.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1015 LAUSANNE
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.