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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Artificial intelligence (AI) can greatly improve healthcare delivery and outcomes, but potential embedded biases can affect fairness in clinical deployment. Here, the authors develop a simulation-based approach to explore which formalisations of AI algorithmic fairness translate into long-term outcome fairness, with a focus on breast cancer.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Health-related traits are known to vary geographically. Here, Amador and colleagues show that regional variation of obesity-related traits in a Scottish population is influenced more by lifestyle differences than it is by genetic differences.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

This description of the Sphagnum (peat moss) genome includes a newly discovered sex chromosome. Interactions among sex, autosomes and environment show direct effects on Sphagnum growth which influences global carbon sequestration.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Two studies illustrate that with the appropriate resources and scale of study, most of the heritability of complex traits in maize is not missing, but can be located within the genome. Given that maize is one of the world's most important crop plants, this has implications for feeding a growing population with minimum carbon footprint as well as for understanding the genetics of complex traits in a range of species.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Drought is a major factor limiting crop productivity. Here, via eQTL analysis and comparative genomics, the authors show compensatory evolution between trans-regulatory loci and transcription factor binding sites that shape the drought response networks in the model C4 grass Panicum hallii.

Analyses of height and body mass index in 119,000 sibling pairs show that linkage and genome-wide association signals colocalize. Further analyses suggest that family-based linkage signals are fully consistent with a highly polygenic architecture.

Heritability estimates provide a useful means of understanding the genetic and environmental contributions to phenotypic variance. The authors define heritability, discuss how to estimate and interpret it in the context of disease and examine how biases in heritability estimates arise.

Parent-of-origin effects (POE) are observed when there are different effects from alleles inherited from the two parents on phenotypic measures. Here, Zeng et al. study POE on DNA methylation in 5,101 individuals and identify genetic variants that associate with methylation variation via POE and their potential phenotypic consequences.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Folkersen et al. report the first results from the SCALLOP consortium, a collaborative framework for pQTL mapping and biomarker analysis of proteins on the Olink platform. A total of 315 primary and 136 secondary pQTLs for 85 circulating cardiovascular proteins from over 30,000 individuals were identified and replicated to yield new insights for translational studies and drug development.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Charles Sawyers and colleagues report that mice expressing a TMPRSS2-ERG fusion develop prostatic intraepithelial neoplasia, but only in the context of PI3-kinase pathway activation mediated by either Pten loss or Akt activation. They also find that human TMPRSS2-ERG–positive tumors are enriched for PTEN loss, suggesting that these two events cooperate in human prostate tumorigenesis.

By day 1,041 after explosion, SN Ia-CSM 2018evt had produced an estimated 0.01 solar masses of dust in the cold, dense shell behind the supernova ejecta–circumstellar medium interaction, ranking it as one of the most prolific dust-producing supernovae ever recorded.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Reversible and rapid switching between metallic and insulating states is key for next-generation memory devices, but identifying and studying such materials is challenging. Here, using angle-resolved photoemission spectroscopy, the authors investigate a metastable metallic state of 1T-TaS₂ when exposed to short current pulses.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Linking epigenetic marks to clinical outcomes promises insight into the underlying processes. Here, the authors introduce a statistical approach to estimate associations between a phenotype and all epigenetic probes jointly, and to estimate the proportion of variation captured by epigenetic effects.

In a phase 1 trial, a lymph node-targeting mutant KRAS peptide vaccine combined with CpG adjuvant is safe, reduces expression of tumor biomarkers and elicits mutant KRAS-specific T cells in patients with pancreatic cancer and colorectal cancer.

Saturation state is shown to be the key component of marine carbonate chemistry affecting larval shell development and growth in two commercially important bivalve species.

Lianas are an important component of tropical forests. Here the authors compare liana and tree functional trait distributions from across the tropics and use a liana-tree competition model to show that a key hydraulic trait influences liana viability and its response to future climate conditions.

Genome-wide association studies have been extensively used to uncover genetic variants that independently influence complex traits, including diseases. This Review describes advances in computational approaches to detect interactions (epistasis) between genetic variants underlying complex traits, including the different promises and pitfalls of the methods. Additionally, the authors summarize current empirical evidence on how pervasive epistasis is in complex traits and its wider biological implications.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The UK Biobank provides data for three depression-related phenotypes. Here, Howard et al. perform a genome-association study for broad depression, probable major depressive disorder (MDD) and hospital record-coded MDD in up to 322,580 UK Biobank participants which highlights excitatory synaptic pathways.