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African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

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.

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.

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).

A study using iPhones and Apple Watches to track and analyze cognitive health over 18 months in more than 23,000 US adults demonstrates the feasibility of remote cognitive health monitoring and uncovers potential methods for early detection of cognitive decline.

The expression of IL1β in triple negative breast cancer (TNBC) has been associated with macrophage-induced immune suppression and cancer progression. Here the authors report that ETS1-driven caspase-1 expression is a feature of TNBC and is required for IL1β-mediated macrophage recruitment and breast cancer growth.

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.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Multiple myeloma (MM) cancer cells can develop different resistance mechanisms to therapies inducing DNA-damage. Here, the authors show that the mitochondrial DNA repair protein DNA2 promotes MM cells survival after DNA damage-induced metabolic reprogramming.

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.

Existing examples of targeted gene insertion in plants either rely on a selectable marker gene or result in short DNA inserts. Here, the authors use an optimized CRISPR-Cas9 method to insert a 5.2 kb carotenoid biosynthesis cassette into genomic safe harbors in rice, and obtain marker-free lines with high carotenoid content.

Predicting which patients will respond to checkpoint blocking therapies is a major challenge. Here the authors score the epigenetic imprinting of T cell responsiveness to type 1 interferons and use this information to predict response to anti-PD1 therapy and long-term survival of cancer patients.

Combination therapy with the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 maintains long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

Although circulating tumour DNA (ctDNA) can predict immune checkpoint blockade (ICB) responses, its association with tumour biomarkers remains unknown. Here, the authors use ctDNA to inform exome and transcriptome profiling of >100 patients with 30 cancer types on a single clinical ICB trial and identify tumour microenvironment features associated with response.

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. Here the authors demonstrate that hematopoietic stem cells with short telomeres induced by mutations affecting telomerase complex genes undergo differentiation towards megakaryopoiesis through the activation of the IFI16-mediated interferon response.

Siu and colleagues use a bespoke ctDNA assay and show predictive utility of longitudinal ctDNA analysis in a phase II clinical trial of patients receiving pembrolizumab that included multiple solid tumor types.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Triggering and sustaining fusion reactions — with the goal of overall energy production — in a tokamak plasma requires efficient heating. Radio-frequency heating of a three-ion plasma is now experimentally shown to be a potentially viable technique.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

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.

Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

Benjamin et al. construct polygenic indexes (DNA-based predictors) for 47 phenotypes and make them available to researchers in 11 datasets. They also present a theoretical framework and estimator to help interpret analyses using polygenic indexes.