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The relation between magnetooptical activity and chirality has previously been confused. Chiral polymer films are presented with state-of-the-art Verdet constants, revealing the role of chirality, and a strategy to enhance the magnetooptical B term.

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

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.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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.

Lovett-Barron et al. register in situ gene expression to cellular-level neural dynamics in behaving zebrafish and find threat-selective populations spanning multiple hypothalamic peptidergic neuron classes, which converge on brainstem defensive action premotor neurons.

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.

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.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

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.

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

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.

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.

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.

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.

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.

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.

MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inform patient enrollment in genomically matched clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Sequencing results of tumor and matched normal tissue from a cohort of >10,000 patients with detailed clinical annotation provide an overview of the genomic landscape of advanced solid cancers and bring new insights into molecularly guided cancer therapy.

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.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

The mechanisms underlying drought-induced tree mortality are not fully resolved. Here, the authors show that, across multiple tree species, loss of xylem conductivity above 60% is associated with mortality, while carbon starvation is not universal.

Candida species are the most common cause of opportunistic fungal infection worldwide. Here, the genomes of six Candida species are sequenced and compared with each other and with related pathogens and non-pathogens; providing insight into the genetic features that underlie the diversity of Candida biology, including pathogenesis and the architecture of mating and meiotic processes.

The authors use two-photon Ca²⁺ imaging of axonal boutons in hippocampal CA1 of behaving mice to monitor the activation of septo-hippocampal GABAergic boutons. They report that some sensory inputs are more effective than locomotion in driving firing by these long-range GABAergic projections.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Analysis of B-cell leukaemia samples reveals that oncogenic mutations do not cause malignant transformation unless they converge on the same signalling pathway, and that it may be possible clinically to combine inhibition of the principal oncogenic driver with reactivation of divergent pathways.

The authors use optical activation and cell type–specific pharmacogenetic silencing in vitro to show that dendritic inhibition critically regulates input-output transformations in mouse hippocampal CA1 pyramidal cells. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata.

The BTK inhibitor ibrutinib is used to treat chronic lymphocytic leukaemia, however some patients develop resistance to the drug. Here, the authors use genomic analyses to examine the clonal evolution of 5 patients that develop resistance to ibrutinib.

Analysis of advanced cancer patients treated with immune-checkpoint inhibitors shows that tumor mutational burden, as assessed by targeted next-generation sequencing, predicts survival after immunotherapy across multiple cancer types.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Crowdsourcing analysis improves computational prediction of cytotoxic responses in humans.

There is a dichotomy in human neuroscience research between task-based cognition and characterization of intrinsic neural patterns (for example, resting-state networks), In this Review, Liu and colleagues discuss a new paradigm for bridging this gap based on decoding of task-related representations.

Transcranial electrical stimulation (tES) can be used in combination with functional MRI (fMRI) to study brain functions. This Consensus Statement provides a checklist for reporting concurrent tES-fMRI research.