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Using hidden genealogical structure to study the architecture of human disease

Project description

Increasing statistical power of genome-wide studies for understanding human diseases

In human genetics, a genome-wide association study usually investigates links between single-nucleotide polymorphism and heritable traits, including predisposition to major diseases. However, the impact of rare genetic variants is poorly understood and current available data and analytical tools are not sufficient to study this class of variation. The goal of the EU-funded ARGPHENO project is to develop new computational methods for evaluation of the phenotypic traits of rare genetic variations. The project will focus on methods for accurate reconstruction of genealogy using sequencing data for subsequent identification of rare genetic variants and their hereditary traits and cross-association with common genetic variants.

Objective

Large-scale genome-wide association studies (GWAS) have yielded thousands of genetic as-sociations to heritable traits, but for most common diseases, these signals collectively explain only a small fraction of phenotypic variation. The phenotypic impact of recent, rare genetic variants, in particular, is poorly understood, but currently available data sets and analytical tools cannot be used to effectively study this class of variation. To address this problem, we propose to develop new computational methodology that will enable studying the phenotypic role of recent, rare genetic variation. This will improve our understanding of the architecture of heritable complex traits, inform the design of future studies, and increase our ability to detect novel associations.

This project will address three specific aims. The first aim is to devise new methods to accurately reconstruct the complex network of genealogical relationships of individuals using high/low-coverage sequencing or microarray data. The second is to leverage these genealogical structures to infer the presence of unobserved genetic variation, with the goal of analyzing variance components of narrow sense heritability attributable to rare variants and studying the evolutionary history of heritable traits. Finally, in the third aim, we will develop new approaches to detect association to both rare and common variants, increasing the statistical power of GWAS methodology.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2019-STG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

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.

€ 1 499 665,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 1 499 665,00

Beneficiaries (1)

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