Volume 54 Issue 6, June 2022

Calls for diversity in genomics have motivated new global research collaborations across institutions with highly imbalanced resources. We describe practical lessons we have learned so far from designing multidisciplinary international research and capacity-building programs that prioritize equity in two intertwined programs — the NeuroGAP-Psychosis research study and GINGER training program — spanning institutions in Ethiopia, Kenya, South Africa, Uganda and the United States.

A new study employs CRISPR–Cas9-based base editing for simultaneous mutagenesis of all copies of histone H3 genes in mammals, highlighting the functional importance of H3K27me3 for Polycomb-mediated gene silencing and the dispensability of H3K27ac in transcriptional activation.

A new study highlights a strategy to link SNPs implicated in human complex traits and diseases with probable causal genes. This method prioritizes genes for functional characterization and helps address questions about the architecture of human phenotypes.

A large-scale single-nucleus chromatin accessibility profiling study in coronary artery samples from patients with coronary artery disease generated a landscape of the regulatory activity during the disease. These data highlight cell type-specific gene programs that can improve the interpretation of human genome-wide association studies findings for cardiovascular diseases.

A study using single-cell transcriptomics and mapping of expression quantitative trait loci (eQTLs) in a dynamic model of CD4⁺ T cell activation reveals novel, context-specific eQTLs linked to genes associated with immune diseases such as inflammatory bowel disease.

CRISPR editing of all 28 alleles encoding histones H3.1, H3.2 and H3.3 in mouse embryonic stem cells (mESCs) generates pan-H3K27R mutant mESCs, which are transcriptionally similar to PRC2-null mESCs. H3K27 acetylation is dispensable for gene derepression in mESCs and for gene activation in epiblast-like cells.

A multiancestry genome-wide association study of chronic alanine aminotransferase elevation identifies candidate risk loci for nonalcoholic fatty liver disease, with replication in external cohorts defined by histology or imaging.

Trans-ancestry genome-wide analyses identify multiple loci associated with ascending aortic diameter. A polygenic score constructed from these loci predicted prevalent risk of thoracic aortic aneurysm in independent populations.

Genome-wide analyses of cardiovascular magnetic resonance images identify variants associated with right ventricular structure and function. Polygenic scores for these traits are associated with dilated cardiomyopathy and coronary artery disease.

Genome-wide analyses of cardiac magnetic resonance imaging data identify loci associated with right heart structure and function. A polygenic predictor of right ventricular ejection fraction is associated with dilated cardiomyopathy risk.

Single-nucleus ATAC-seq characterization of chromatin accessibility in human coronary artery disease samples identifies cell-type- and state-specific regulatory mechanisms underlying disease risk, highlighting the roles of TBX2 and PRDM16.

Single-cell RNA sequencing of CD4⁺ naive and memory T cells from 119 individuals generates an expression quantitative trait locus (eQTL) map during T cell activation, identifying 6,407 eQTL genes, including 2,265 that are dynamically regulated.

A heritability-based framework for evaluation of SNP-to-gene linking methods is used to construct an optimal, combined approach and applied to 49 traits. Analysis of trait omnigenicity suggests gene-level architecture varies depending on variant frequency.

Allelic imbalance analysis applied to ATAC-Seq data from 23 cancer types identifies 7,262 allele-specific accessibility quantitative trait loci, which are enriched for cancer risk heritability and altered transcription factor binding motifs.

A genomic analysis of ductal carcinoma in situ (DCIS) samples with matched ipsilateral invasive breast cancer recurring later shows that around 18% of tumors were unrelated to the DCIS, and had distinct clonal origins.

SMARCE1 loss destabilizes the canonical BAF complex and increases the formation of BRD9-containing non-canonical (ncBAF) complexes. SMARCE1-deficient cells, which are a model for clear cell meningioma, are sensitive to ncBAF complex inhibition.

NFIA and NFIX directly repress the expression of fetal-type β-globin-like genes HBG1 and HBG2 in adult erythroid cells, and also do it indirectly through the upregulation of BCL11A.

A high-quality autopolyploid genome of Saccharum spontaneum accession Np-X and resequencing of 102 accessions provide insights into the recent chromosome reduction and polyploidization in Saccharum.

snipar is a software package for imputing missing parental genotypes and estimating direct genetic effects. Application to UK Biobank data shows that effects estimated by standard genome-wide association study designs have confounding bias for some phenotypes.