Fine-mapping genetic associations

Abstract Whilst thousands of genetic variants have been associated with human traits, identifying the subset of those variants that are causal requires a further ‘fine-mapping’ step. We review the basic fine-mapping approach, which is computationally fast and requires only summary data, but depends...

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Bibliographic Details
Published in:Human molecular genetics 2020-09, Vol.29 (R1), p.R81-R88
Main Authors: Hutchinson, Anna, Asimit, Jennifer, Wallace, Chris
Format: Article
Language:English
Subjects:
Chromosome Mapping - methods
Disease - genetics
Genetic Markers
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study - methods
Humans
Invited Review
Linkage Disequilibrium
Models, Genetic
Polymorphism, Single Nucleotide
Quantitative Trait Loci
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Summary:Abstract Whilst thousands of genetic variants have been associated with human traits, identifying the subset of those variants that are causal requires a further ‘fine-mapping’ step. We review the basic fine-mapping approach, which is computationally fast and requires only summary data, but depends on an assumption of a single causal variant per associated region which is recognized as biologically unrealistic. We discuss different ways that the approach has been built upon to accommodate multiple causal variants in a region and to incorporate additional layers of functional annotation data. We further review methods for simultaneous fine-mapping of multiple datasets, either exploiting different linkage disequilibrium (LD) structures across ancestries or borrowing information between distinct but related traits. Finally, we look to the future and the opportunities that will be offered by increasingly accurate maps of causal variants for a multitude of human traits.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddaa148