Trans-Ethnic Fine-Mapping of Rare Causal Variants View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2015

AUTHORS

Xu Wang , Yik-Ying Teo

ABSTRACT

Genome-wide association studies (GWAS) have achieved great success in identifying genetic variants that are associated with complex diseases and human traits. However, the findings thus far have mostly been limited to variants that are present at more than 5 % frequency in the population. Even when considered jointly, these variants generally explain only a small proportion of the disease heritability, especially since they are mostly tagging single nucleotide polymorphisms (SNPs) that are correlated, often imperfectly, with the underlying causal variants that are functionally responsible for influencing disease susceptibility. Identifying these causal variants or localizing the genomic regions where the causal variants can be found is a process termed as fine-mapping. While stretches of long linkage disequilibrium (LD) in the human genome have benefitted the discovery of phenotype-associated tagging SNPs, it has paradoxically hampered the process of identifying the functional mutations as they cannot be distinguished from perfect or near-perfect surrogates. Trans-ethnic fine-mapping is a process that relies on disparate LD patterns in populations of diverse genetic ancestries to localize the causal variants, and this has been successfully implemented to fine-map several common GWAS findings. The focus for the next phase in discovering genotype–phenotype associations has shifted to mapping variants that are present at less than 5 % frequency in the population, broadly categorized as low-frequency and rare variants. However, it is not clear if the process of trans-ethnic fine-mapping be similarly applicable to identify these low frequency or rare causal variants. In this chapter, we will explore the feasibility of trans-ethnic fine-mapping of rare causal variants by investigating the conditions that have made the process possible for common variants and whether these conditions are present for rare variant analyses. More... »

PAGES

253-261

Book

TITLE

Assessing Rare Variation in Complex Traits

ISBN

978-1-4939-2823-1
978-1-4939-2824-8

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-1-4939-2824-8_18

DOI

http://dx.doi.org/10.1007/978-1-4939-2824-8_18

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053667796


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