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Histological analysis of the human pancreas provides insight into initiation and progression of type 1 diabetes (T1D). Here the authors utilize pancreatic tissue sections across different disease stages and apply whole slide imaging and digital pathology to identify endocrine cell composition, immune cell burden and spatial islet relationships in health and over the course of T1D.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Implementation of organized low-dose computed tomography screening in over 4,000 individuals with high risk for lung cancer as part of the Ontario Lung Cancer Screening Pilot reported high cancer detection rates, early detection of cancer and low serious harms.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Lung cancer is the commonest cancer globally. Reflecting patterns of smoking and other risk factor exposures, both the incidence of and mortality from lung cancer are highest in economically developed countries. Nonetheless, developing and less economically developed countries are likely to have the biggest increases in lung cancer in the coming years. In this Review, the authors describe the global epidemiology of lung cancer, and how changes in exposures, socioeconomic status, public health interventions and better treatment strategies are influencing both the incidence of and mortality from lung cancer.

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.

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.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

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.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Kvarven, Strømland and Johannesson compare meta-analyses to multiple-laboratory replication projects and find that meta-analyses overestimate effect sizes by a factor of almost three. Commonly used methods of adjusting for publication bias do not substantively improve results.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

During wound induced hair follicle neogenesis (WIHN), stem cells regenerate hair follicles but how this arises is unclear. Here, the authors show that self-noncoding dsRNA activates the antiviral receptor TLR3 to induce intrinsic retinoic acid, which stimulates WIHN in mice, and in isolated human keratinocyte cells.

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.

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.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

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.

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.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

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.

The UN 2030 Agenda for Sustainable Development recognizes the need to transform governance for the world to develop sustainably. Using a mixed method approach, this study presents 13 principles for transformative ocean governance that can help turn ocean-use practices into more sustainable ones.

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.

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.

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.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

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.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Ibogaine is a natural substance that interrupts opioid addiction but has cardiac risks. This article introduces novel ibogaine analogs that show reduced cardiac risk and enhanced neuroplasticity and therapeutic-like effects in models of opioid use disorder.

An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.

The degree to which species tolerate human disturbance contributes to shape human-wildlife coexistence. Here, the authors identify key predictors of avian tolerance of humans across 842 bird species from open tropical ecosystems.

The heterogeneity of whole-exome sequencing (WES) data generation methods presents a challenge to joint analysis. Here, the authors present a bioinformatics strategy to generate high-quality data from processing diversely generated WES samples, as applied in the Alzheimer’s Disease Sequencing Project.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer.