Browse Articles

Post-prediction genome-wide association study (POP-GWAS) is a statistical framework that uses summary statistics from labeled samples with both observed and imputed phenotypes to debias single-nucleotide polymorphism effect size estimates for unlabeled samples with imputed phenotypes only, leading to valid and powerful inference.

Large-scale multivariate analyses across populations of European ancestry identify risk loci for the metabolic syndrome, improving polygenic prediction models and highlighting associations with diverse traits beyond cardiometabolic diseases.

The mammalian inactive X chromosome shows unusual folding dominated by large-scale structures. A study finds a megadomain structure with a boundary at the Xist locus, preceding the well-known Dxz4-separated megadomains in somatic cells.

Primary cell cultures need to be frequently passaged, which limits the study of long-term biological processes, such as how mutant clones colonize aging epithelia. Esophageal epithelioids self-maintain for months, recapitulating progenitor cell behavior in vivo. Epithelioid CRISPR–Cas9 screens reveal genes encoding molecules that control cell fitness.

We identified methylated tandem repeat expansions that resemble the FMR1 CGG repeat that causes fragile X syndrome and investigated their association with traits in the UK Biobank. AFF3 expansion carriers had a 2.4-fold reduced probability of completing secondary education and were enriched in a cohort of individuals with intellectual disability.

A co-factor for the androgen receptor, NSD2, provides insights into context-specific functions of the androgen receptor and is a new target for intervention.

This study presents a spatial transcriptomic analysis of matched primary tumors, liver metastases and lymph node metastases from patients with pancreatic ductal adenocarcinoma. Using a tumor ecosystem approach, we uncovered notable tumor microenvironmental heterogeneity and marked differences between primary and metastatic samples, providing key insights into metastatic pancreatic cancer.

Somatic mutations accrue with age as patches of mutant clones arise in otherwise histologically normal tissue. The clones’ persistence, expansion and roles in physiology and tumorigenesis are unclear. New work on the behavior of Pik3caH1047R mutant esophageal clones shows that host-dependent metabolic features underpin their expansion.

Polygenic scores (PGSs) have transformed human genetic research and have numerous potential clinical applications. Here we present a series of recent enhancements to the PGS Catalog and highlight the PGS Catalog Calculator, an open-source, scalable and portable pipeline for reproducibly calculating PGSs that democratizes equitable PGS applications.

GeNA identifies cell-state abundance quantitative trait loci (csaQTLs) in single-cell RNA sequencing data. Applied to OneK1K, GeNA identifies natural killer cell and myeloid csaQTLs and implicates interferon-α-related cell states using a polygenic risk score for systemic lupus erythematosus.

Comparison of association signals in UK Biobank using different strategies for assessing genetic variation shows that whole-exome sequencing combined with array genotyping and imputation offers similar performance to whole-genome sequencing at a reduced cost.

Deep rare variant association testing (DeepRVAT) is a deep set neural network model that flexibly integrates rare variant annotations into a trait-agnostic gene impairment score. These scores improve association testing and polygenic risk prediction.

Statistical fine-mapping of mRNA and protein quantitative trait loci in blood samples from the Japan COVID-19 Task Force sheds light on regulatory mechanisms and disease associations.

Phylogenetic analysis of trait heritability (PATH) applies phylogenetic correlations to single-cell lineage tracing data, quantifying cell state plasticity and transition probabilities. PATH offers insights into cell state heritability and transition dynamics in cancers.

Phenome-wide analysis in the UK Biobank identifies GC-rich tandem repeat expansions associated with a range of traits, including a GCC expansion in AFF3 contributing to intellectual disability.

Epithelioids are genetically stable, self-sustaining three-dimensional cultures. They may be used to investigate various aspects of epithelial biology over several months without need for passaging. In this paper, mouse epithelioids are used to identify drivers of clonal expansion in the esophagus.

Analysis of autosomal recessive coding variants in 29,745 trios from the DDD study and GeneDx provides insights into the genetic architecture of developmental disorders across ancestrally diverse populations.

Blockade of primary genomic binding sites with small molecules causes redistribution of the transcription factor PU.1 to alternative binding sites; its transcriptional activity at these sites activates secondary gene networks that drive myeloid cell differentiation.

A large-scale multi-ancestry genome-wide association study of European, African, admixed American, South Asian and East Asian ancestries provides insights into the pathogenesis of anxiety disorders.