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A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Serum neutralizing antibody titers against the SARS-CoV-2 Omicron variant markedly increase after a third dose of BNT162b2 vaccine in individuals who previously received either two doses of the BNT162b2 vaccine or two doses of the CoronaVac vaccine.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Acquired resistance to cancer therapies can develop due to kinase rewiring. Here, using a broad-spectrum chemical probe, the authors perform kinome screening and identify CDK6-mediated accumulation of cancer stem cells as a driver of lenvatinib (multitargeted tyrosine kinase inhibitor) resistance in hepatocellular carcinoma.

Jellyfish plays an important ecological role in surface waters and the deep sea. Here the authors report genome sequences of two true jellyfish, Sanderia malayensis and Rhopilema esculentum, showing distinct homeobox gene clusters and sesquiterpenoid pathway.

There are adverse events associated with COVID-19 vaccines, such as myocarditis for adolescents following receipt of SARS-CoV-2 mRNA vaccines. Here the authors compare the immunogenicity and reactogenicity of two widely available SARS-CoV-2 vaccines (BNT162b2, an mRNA vaccine, and CoronaVac, a whole-virus inactivated vaccine) in healthy adolescents.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

A metabolic modeling approach reveals druggable host cell pathways essential for viral replication across various viruses with minimal cytotoxicity. These findings highlight cellular metabolism as a promising target for antiviral therapy.

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.

Governance inefficiencies threaten the potential of smart city projects to deliver equitable urban transformations. Current strategies often hinder implementation, and risk harmful technological effects on communities. Tackling this challenge demands urgent reforms to better integrate scientific insights into smarter governance practices.

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).

Chow et al. show that high blood levels of insulin in prediabetic conditions are linked to saturated insulin levels in the brain. Chronic insulin exposure leads to insulin resistance, cell cycle reentry and premature aging, corresponding to senescence-like pathological changes in neurons.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

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.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Immune responses to pancreatic ductal adenocarcinoma can be inhibited by cancer cells. Here the authors show that high levels of progranulin in PDAC inhibits immune responses by reducing MHC class I antigen presentation through enhanced degradation of MHC class I via autophagy.

Tools for gaining long-term genetic access to mu-opioid receptor (MOR) neural cell types are limited. Here, the authors develop a suite of adeno-associated viral tools allowing selective genetic access to MOR cell types, and showcase their use across species.

A direct search for effective electromagnetic interactions between dark matter and xenon nuclei that produce a recoil of the latter is carried out and the first constraint on charge radius of dark matter is derived.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Sniffles2 detects mosaic structural variation from bulk long-read sequencing data.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Mechanical flexibility gives organic ferroelectric materials a potential advantage over their inorganic counterparts, yet it is challenging to produce them. Owczareket al. report flexible crystals based on trisubstituted haloimidazoles that show both ferroelectric and piezoelectric properties.

Block copolymer self-assembly can successfully generate monolayers of complex nanopatterns. Here, the authors orthogonally self-assemble 2 or 3 layers of distinct molecular weight block copolymers, and fabricate complex nanomesh structures without alignment or high-resolution lithographic templating.