Department of Biology, Stanford University, Stanford, United States.
Department of Computer Science, Stanford University, Stanford, United States.
Elife. 2019 Jan 16;8:e39595. doi: 10.7554/eLife.39595.
Genome-wide association studies (GWAS) are a powerful approach for connecting genotype to phenotype. Most GWAS hits are located in cis-regulatory regions, but the underlying causal variants and their molecular mechanisms remain unknown. To better understand human -regulatory variation, we mapped quantitative trait loci for chromatin accessibility (caQTLs)-a key step in cis-regulation-in 1000 individuals from 10 diverse populations. Most caQTLs were shared across populations, allowing us to leverage the genetic diversity to fine-map candidate causal regulatory variants, several thousand of which have been previously implicated in GWAS. In addition, many caQTLs that affect the expression of distal genes also alter the landscape of long-range chromosomal interactions, suggesting a mechanism for long-range expression QTLs. In sum, our results show that molecular QTL mapping integrated across diverse populations provides a high-resolution view of how worldwide human genetic variation affects chromatin accessibility, gene expression, and phenotype.
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).
全基因组关联研究（GWAS）是一种将基因型与表型联系起来的强大方法。大多数 GWAS 命中都位于顺式调控区域，但潜在的因果变异及其分子机制仍不清楚。为了更好地了解人类调控变异，我们在来自 10 个不同人群的 1000 个人中绘制了染色质可及性的数量性状基因座（caQTLs）图谱——这是顺式调控的关键步骤。大多数 caQTLs 在人群中是共享的，这使我们能够利用遗传多样性来精细映射候选因果调节变异，其中有数千个先前与 GWAS 有关。此外，许多影响远端基因表达的 caQTLs也改变了长距离染色体相互作用的景观，这表明了长距离表达 QTL 的一种机制。总之，我们的结果表明，跨多种人群进行的分子 QTL 图谱绘制提供了一个高分辨率的视角，展示了全球人类遗传变异如何影响染色质可及性、基因表达和表型。
本文经过编辑过程，作者决定如何回应同行评审期间提出的问题。审稿编辑的评估是仍然存在未解决的小问题（见评审意见）。
