Search

Ossenkoppele, Salvado et al. show that plasma p-tau217 and tau-PET predict cognitive decline equally well among cognitively unimpaired individuals. Their combined use further boosts prognostic accuracy. A sequential approach can enhance precision and efficiency of preclinical Alzheimer trials.

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.

Ossenkoppele, Coomans and colleagues analyzed the tau PET data of 12,048 individuals from 42 cohorts worldwide. They found that age, amyloid-β status, presence of an APOE ε4 allele and female sex are key contributors to tau PET positivity, which should aid clinical decision-making and trial designs.

This large integrated analysis of the KRAS^G12C inhibitor sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 trials shows that low expression of TTF-1 and high expression of NRF2 determine anti-tumor efficacy of sotorasib in non–small-cell lung cancer.

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.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

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.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

In the final analysis of a phase 1 trial evaluating a lymph node-targeting mutant KRAS peptide vaccine combined with CpG in the adjuvant setting for patients with KRAS mutant pancreatic or colorectal cancer, median relapse-free survival and overall survival were not reached for patients with robust antigen-specific T cell responses, and these responses were durable with evidence of antigen spreading.

Cardiovascular and metabolic risk factors (CVM) impact brain structure and increase dementia risk. Here, the authors developed and validated machine learning models to measure the neuroanatomical changes in people with cardiovascular and metabolic diseases that are cognitively unimpaired.

Feizpour et al. assess the utility of a high-performing Alzheimer’s disease (AD) blood test to discriminate AD disease stages. The blood test reliably detects Intermediate and Advanced stages of disease, and while the test is less effective at distinguishing Advanced stage alone, it may reduce reliance on expensive brain scans.

Therapeutic antibody patent owners face continuing challenges trying to obtain broad patents and enforce them in the United States and Europe.

A phase 2 randomized controlled trial of ustekinumab in 72 adolescents with recent-onset type 1 diabetes showed that treatment was well tolerated and β-cell function was 49% higher in the intervention group compared to the placebo arm after 12 months.

Accurate prediction of disease progression in Alzheimer’s disease (AD) is necessary for optimal recruitment of patients to clinical trials. Here, the authors present AD Course Map, a statistical model which helps to predict disease progression in participants, thus decreasing the required sample size for a hypothetical trial.

Results from the phase 2/3 clinical trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease reveal no beneficial effects on cognitive measures despite a significant reduction in amyloid plaques and other key biomarkers in those treated with gantenerumab.

In a phase 1b trial, treatment of patients with muscle-invasive bladder cancer with intravesical oncolytic virus cretostimogene grenadenorepvec in combination with nivolumab was safe and led to encouraging preliminary clinical response rates.

Environmental DNA from unculturable microorganisms contains genes with useful functions that remain difficult to identify and isolate. Here Colin, Kintses et al.demonstrate the screening of millions of samples in pL volumes to directly identify new enzymatic activities and complements sequence-based approaches.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Assessing brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies, a generative model identifies five dominant patterns of brain atrophy, with specific associations with biomedical, lifestyle and genetic factors.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

This Resource presents the genetic subset of the 136,000 chemical and genetic perturbations tested by the Joint Undertaking for Morphological Profiling (JUMP) Cell Painting Consortium and associated analysis of phenotypic profiles.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

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 Qiita web platform provides access to large amounts of public microbial multi-omic data and enables easy analysis and meta-analysis of standardized private and public data.

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

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

A meta-analysis of individual-level patient data from 66 clinical studies supports the utility of glomerular filtration rate as a surrogate endpoint in clinical trials for chronic kidney disease, with potential to enable detection of events earlier in the disease course.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

In a phase 1 trial, a lymph node-targeting mutant KRAS peptide vaccine combined with CpG adjuvant is safe, reduces expression of tumor biomarkers and elicits mutant KRAS-specific T cells in patients with pancreatic cancer and colorectal cancer.

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Alzheimer's disease is a progressive, neurodegenerative disorder that affects 10–30% of people >65 years of age. In this Primer, Masters and colleagues describe the pathophysiology of Alzheimer's disease, the advances in diagnostic biomarkers, and the current and future management options.

The millimetre image of the Centaurus A nucleus by the Event Horizon Telescope reveals a highly collimated, asymmetrically edge-brightened jet. The source’s event horizon shadow should be visible at terahertz frequencies, consistent with the universal scale invariance of black holes.