From GWAS to function: using functional genomics to identify the mechanisms underlying complex diseases

E Cano-Gamez, G Trynka - Frontiers in genetics, 2020 - frontiersin.org
Genome-wide association studies (GWAS) have successfully mapped thousands of loci
associated with complex traits. These associations could reveal the molecular mechanisms …

Towards a comprehensive catalogue of validated and target-linked human enhancers

M Gasperini, JM Tome, J Shendure - Nature Reviews Genetics, 2020 - nature.com
The human gene catalogue is essentially complete, but we lack an equivalently vetted
inventory of bona fide human enhancers. Hundreds of thousands of candidate enhancers …

Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens

JA Morris, C Caragine, Z Daniloski, J Domingo, T Barry… - Science, 2023 - science.org
Most variants associated with complex traits and diseases identified by genome-wide
association studies (GWAS) map to noncoding regions of the genome with unknown effects …

Combining SNP-to-gene linking strategies to identify disease genes and assess disease omnigenicity

S Gazal, O Weissbrod, F Hormozdiari, KK Dey… - Nature Genetics, 2022 - nature.com
Disease-associated single-nucleotide polymorphisms (SNPs) generally do not implicate
target genes, as most disease SNPs are regulatory. Many SNP-to-gene (S2G) linking …

Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations

CP Fulco, J Nasser, TR Jones, G Munson… - Nature …, 2019 - nature.com
Enhancer elements in the human genome control how genes are expressed in specific cell
types and harbor thousands of genetic variants that influence risk for common diseases …

The allelic landscape of human blood cell trait variation and links to common complex disease

WJ Astle, H Elding, T Jiang, D Allen, D Ruklisa… - Cell, 2016 - cell.com
Many common variants have been associated with hematological traits, but identification of
causal genes and pathways has proven challenging. We performed a genome-wide …

Current challenges in understanding the role of enhancers in disease

JB Zaugg, P Sahlén, R Andersson… - Nature structural & …, 2022 - nature.com
Enhancers play a central role in the spatiotemporal control of gene expression and tend to
work in a cell-type-specific manner. In addition, they are suggested to be major contributors …

Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases

EM Weeks, JC Ulirsch, NY Cheng, BL Trippe, RS Fine… - Nature …, 2023 - nature.com
Genome-wide association studies (GWASs) are a valuable tool for understanding the
biology of complex human traits and diseases, but associated variants rarely point directly to …

Multiple causal variants underlie genetic associations in humans

NS Abell, MK DeGorter, MJ Gloudemans, E Greenwald… - Science, 2022 - science.org
Associations between genetic variation and traits are often in noncoding regions with strong
linkage disequilibrium (LD), where a single causal variant is assumed to underlie the …

Ribosome levels selectively regulate translation and lineage commitment in human hematopoiesis

RK Khajuria, M Munschauer, JC Ulirsch, C Fiorini… - Cell, 2018 - cell.com
Blood cell formation is classically thought to occur through a hierarchical differentiation
process, although recent studies have shown that lineage commitment may occur earlier in …