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A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

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).

The Sc2.0 project involved synthesis and debugging of 16 chromosomes, and a tRNA neochromosome. Here the authors descript the SynXVI project, accompanied by an analysis of how similar projects could operate with hindsight and newly available technologies, and lessons learned from Sc2.0.

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.

The neurobiology of human brain development and aging is hard to study in vivo. The authors report on distinct spatial associations between brain morphology and cellular as well as molecular brain properties throughout neurodevelopment and aging.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Here, the authors use paleogenomic data from the indigenous people of the Canary Islands to shed light on the Prehistory of North Africa, and on how insularity and resources availability shaped the genetic composition of this isolated population.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Analyses of imputed ancient genomes and of samples from the UK Biobank indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

Long COVID or post-acute sequelae of SARS-CoV-2 is defined by persisting chronic symptoms following acute SARS-CoV-2 infection but represent an aetiologically diverse group of disorders. Here authors identify molecularly distinct subtypes, including a form with persistent inflammation, via longitudinal analysis of serum proteome.

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.

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.

Ancient DNA analyses reveal that Viking Age migrations from Scandinavia resulted in differential influxes of ancestry to different parts of Europe, and the increased presence of non-local ancestry within Scandinavia.

Series of machine learning models, relevant for tasks in biology, medicine, and finance, usually involve complex feature attribution techniques. The authors introduce a tractable method to compute local feature attributions for a series of machine learning models inspired by connections to the Shapley value.

Nanowire networks with memristive properties are promising for neuromorphic applications. Here, the authors observe the formation of a preferred conduction pathway which uses the lowest possible energy to get through the network and could be exploited for the design of optimal brain-inspired devices.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

An epicardial device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to the epicardium provides therapeutic benefits in a rat model of myocardial infarction.

Tree-based machine learning models are widely used in domains such as healthcare, finance and public services. The authors present an explanation method for trees that enables the computation of optimal local explanations for individual predictions, and demonstrate their method on three medical datasets.

Ensembles of explainable machine-learning models increase the quality of explanations for the molecular basis of synergetic drug combinations, as shown for the treatment of acute myeloid leukaemia.

It is found that carbon export fluxes to the deep ocean from a highly productive, naturally iron-fertilized region of the sub-Antarctic Southern Ocean are two to three times larger than the carbon export fluxes from an adjacent high-nutrient low-chlorophyll area not fertilized by iron. These findings support the hypothesis that increased iron supply to the glacial sub-Antarctic may have directly enhanced carbon export to the deep ocean.

The competitive dynamics of mitochondrial haplotypes juxtaposed within the same cell are poorly studied. Here the authors show, in the context of a transmissible cancer, that one haplotype has recurrently entered cancer cells by horizontal transfer and appears to have a ‘selfish’ selective advantage.

Investigations of an Icelandic volcanic eruption confirm that sulfate aerosols caused a discernible yet transient brightening effect, as predicted, but their effect on the liquid water path was unexpectedly negligible.

Himalayan valley-floor widths are controlled by long-term tectonically driven exhumation, rather than by water discharge, according to an analysis of valley-floor width and exhumation rate observations.

Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6.

Dominic Kwiatkowski and colleagues of the MalariaGEN and the WTCCC consortiums report a genome-wide analysis of severe malaria in The Gambia. They provide guidance for design of GWAS in African populations, and demonstrate the usefulness of multipoint imputation based on population-specific sequencing data.