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The mechanisms underlying many genetic variants associated with human traits are often unknown. Here, the authors identify the developmental stage-, organ-, tissue- and cell type-specific associations between genetic variation and gene expression in cardiac tissues, and describe how these associations affect complex cardiac traits and disease.

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Here, authors show that pluripotency and self-renewal processes have a high level of regulatory complexity and suggest that genetic factors contribute to cell state transitions in human iPSC lines.

Genetic variation associated with gene expression changes has mostly been studied in the context of single nucleotide variants. Here, Jakubosky et al. report eQTL analysis of structural variants and short tandem repeats and find properties, such as length of variation, that affect the association.

The complexity of structural variation (SV) and short tandem repeats (STRs) makes it necessary to apply different calling and filtering strategies to sequencing datasets. Here, Jakubosky et al. report a comprehensive SV and STR callset from whole-genome sequencing of 477 individuals from iPSCORE and HipSci using five algorithms.

Fetal development plays an important role in defining adult diabetes risk. Here, authors identified a genetic link between fetal pancreatic gene expression, obesity, and diabetes risk through eQTL mapping of iPSC-derived pancreatic progenitor cells.

Cellular heterogeneity can confound functional genomics analyses of bulk tissues. Here, Donovan et al. deconvolute bulk GTEx RNA-seq data utilizing scRNA-seq data from the Tabula Muris project and show the power of using cell populations in eQTL analyses to identify disease and cell-type-associated regulatory variants.

Cancer driver mutations can occur within noncoding genomic sequences. Here, the authors develop a statistical approach to identify candidate noncoding driver mutations in DNase I hypersensitive sites in breast cancer and experimentally demonstrate they are regulatory elements of known cancer genes.

Analysis of iPSC-derived cardiomyocytes identifies variants associated with allele-specific effects on NKX2-5 binding. Fine-mapping and functional studies suggest that such variants underlie cardiac-specific expression quantitative trait loci and associations with electrocardiographic traits.

Identifying driver genes in unstable, heterogenous tumour types can be challenging. Here, Mourikis, Benedetti, Foxall and colleagues present a machine learning algorithm to tackle this problem in esophageal adenocarcinoma.

It is currently unclear how quantitative changes in chromatin loop propensity contribute to differential gene regulation. Here, the authors use phased Hi-C, RNA-seq, and ChIP-seq to show that subtle changes in loop propensity associate with differential gene regulation across cell types and haplotypes.

The dearth of glioblastoma model systems that accurately recapitulate the disease remains a challenge. Here, the authors develop cancer avatars using genetically engineered human induced pluripotent cells.

PTEN mutations are frequent in glioblastoma and often are associated with therapeutic resistance. Here, the authors demonstrate that PTEN regulates gene expression at the chromatin level by interacting with the histone chaperone DAXX and H3.3, and that DAXX inhibition inhibits PTEN-deficient GBM growth in vivo.

Integrative data analysis of 1,367 human iPSC lines maps common and rare regulatory variants that colocalize with loci associated with human traits and diseases.

Disruption of a promoter can release its partner enhancer to activate other promoters in the same contact domain, and this process, named ‘enhancer release and retargeting’, can often lead to gene alterations that cause disease.

Transcriptional changes during prostate cancer progression are not yet fully understood. Here, the authors integrate a transcriptomics atlas of prostate cancer and validate it with preclinical models and single-cell RNA-seq, revealing the role of EZH2 and macrophage polarisation in tumour progression.