Fine-mapping cis-regulatory variants in diverse human populations.

Ashley Tehranchi,Irene Kaplow,Michael Dacre,Brian Hie,Peter Combs,Hunter B Fraser,Kade Pettie

doi:10.7554/elife.39595

Abstract

This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter).

Highlights

Genome-wide association studies (GWAS) have been instrumental in advancing our understanding of complex traits
Genetic variants that affect chromatin accessibility (CA) in cis will cause the more accessible allele to increase in frequency after ATAC compared to before, whereas variants with no effect on accessibility will have no significant change in frequency (Figure 1A)
We selected a total of 1000 lymphoblastoid cell lines (LCLs) with full genome sequences (Auton et al, 2015) from 10 diverse populations: four European, four African, one African-American, and one Han Chinese (Figure 1A, Figure 1—source data 1)

Summary

Introduction

GWAS have been instrumental in advancing our understanding of complex traits These studies have successfully mapped thousands of loci associated with hundreds of human diseases and other traits (Eicher et al, 2015). Shared causal variants should be consistently associated with a trait across populations, while tag SNPs—those associated only because of their LD with a causal variant—may only be associated in a subset of populations, due to differing LD structures. This approach is especially effective when combining populations with disparate LD patterns, such as Europeans and Africans (Asimit et al, 2016). Most GWAS have been restricted to European cohorts, limiting their mapping resolution, and their ability to predict disease risk in non-European individuals (Hindorff et al, 2018)

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Conclusion