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We model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids, the results implying predictability in the earliest stages of tumorigenesis.

Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

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 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.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Eczema may be associated with atopic as well as non-atopic diseases. Here the authors studied associations between atopic eczema and 71 subsequent adverse health outcomes in a large (>20 million) UK primary care data, enabling comparison between outcomes and judging relevance for clinical practice and guidelines.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

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.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.

The effectiveness of community-based land protection compared to traditional top-down protection is debated. Here, the authors show that both community-managed forests and traditional protected areas in Madagascar experienced deforestation during a political crisis but the former were especially vulnerable in the post-crisis period.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

This study shows that conserving approximately half of global land area through protection or sustainable management could provide 90% of ten of nature’s contributions to people and could meet representation targets for 26,709 species of mammals, birds, amphibians, and reptiles. This finding supports recent commitments to conserve at least 30% of global lands and waters by 2030.

Haploinsufficiency in three genes associated with risk of autism spectrum disorder—KMT5B, ARID1B and CHD8—in cell lines from multiple donors results in cell-type-specific asynchronous development of GABAergic neurons and cortical deep-layer excitatory projection neurons.

A systematic census at 1,636 sites around Australia from 2008 to 2021 finds that more than 30% of shallow invertebrate species in cool latitudes exhibit a high extinction risk due to declining populations and oceanic barriers, but tropical coral species remain relatively stable.

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.

Protected areas are meant to defend species from direct exploitation and habitat loss, but they might also reduce climate change impacts. Here, the authors show that marine protected areas mitigate the impacts of marine heatwaves on reef fish communities.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

The marine environment is under threat from climate change. This study finds that marine reserves can maintain biodiversity and abundance of large-bodied individuals in a warming environment. They also protect against colonization by range-shifting species when compared with fished sites.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

CV2CoV, a second-generation mRNA COVID-19 vaccine with non-modified nucleosides but optimized non-coding regions, is demonstrated to be effective against SARS-CoV-2 challenge when tested in non-human primates.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 in rhesus macaques.

Dysregulation of the post-translational modification neddylation has been implicated in liver diseases such as fibrosis and hepatocellular carcinoma. Here the authors report that hepatic neddylation deficiency via genetic deletion of NEDD8 Activating Enzyme E1 Subunit 1 (NAE1) causes acute liver failure due to mitochondrial dysfunction and aberrant activation of NF-κB-inducing kinase in mice.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

How the 22q11.2 deletion predisposes to psychiatric disease is unclear. Here, the authors examine living human neuronal cells and show that 22q11.2 regulates the expression of genes linked to autism during early development, and genes linked to schizophrenia and synaptic biology in neurons.

In extinct species including non-avian dinosaurs, bone density is shown to be a reliable indicator of aquatic behavioural adaptations, which emerged in spinosaurids during the Early Cretaceous.

SARS-CoV-2 challenge of rhesus macaques demonstrates that the Ad26.COV2.S vaccine induces robust protection against both the WA1/2020 isolate and the B.1.351 variant of concern.

Using a species generalization index calculated from a global dataset of reef fishes and their habitats, the authors show that generalist species respond more successfully to habitat disruption and are better able to move polewards in response to climate change.

How marine communities will respond to climate change depends on the thermal sensitivities of existing communities; existing reef communities do not show a perfect fit between current temperatures and the thermal niches of the species within them and this thermal bias is a major contributor to projected local species loss.

Most tumours associated with germline BRCA1/BRCA2 loss of function mutations respond to DNA damaging agents, however, some do not. Herein, the authors identify that a subset of breast/ovarian tumors retain a normal allele, which is associated with decreased overall survival after DNA damage-inducing platinum chemotherapy.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

A set of three papers in Nature reports a new proteomics resource from the UK Biobank and initial analysis of common and rare genetic variant associations with plasma protein levels.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

This study shows that most known mediators of immunity, such as TLR2, MyD88, T cells or B cells, and neutrophils and monocytes, are dispensable for pain produced by Staphylococcus aureus infection; instead, bacterial products, such as N-formylated peptides and α-haemolysin, induce pain by directly activating nociceptor neurons, which in turn modulate inflammation.

A study of more than one million 23andMe research participants identifies genetic and nongenetic associations with COVID-19 susceptibility and severity.