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Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.

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.

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 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.

Machine learning can be used to identify subtypes of psychiatric disease. Here the authors identified two neurostructural subgroups in schizophrenia, each showing reproducibility and generalizability across different collection locations and illness stages, using the SuStain algorithm.

Metastasis of urothelial carcinoma remains incurable due to insufficient treatment options for advanced disease. Here, the authors combine whole exome sequencing and RNA-seq from metastatic biopsies, and show temporal evolution when compared with primary tumour.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

This work demonstrates a novel preimplantation genetic testing (PGT) method that detects aberrations in both the nuclear and mitochondrial genomes of IVF embryos. The technology traces the origin of chromosomal aberrations to before or after fertilisation.

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.

Exploratory biomarker analyses of the phase 3 CheckMate 649 trial show that in patients with advanced gastroesophageal cancer, KRAS alterations were associated with greater overall survival (OS) benefit when treated with nivolumab plus chemotherapy vs chemotherapy alone, whereas high regulatory T-cell signatures were associated with greater OS benefit when treated with nivolumab plus ipilimumab.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

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.

Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

White matter hyperintensities are linked to cortical atrophy, a key feature in dementia. Here, the authors identify loci associated with cortical atrophy related to white matter hyperintensities, which involve vascular and neuronal processes.

The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

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.

Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

In an ongoing adaptive-design trial exploring different combinations of neoadjuvant immunotherapies including the anti-PD-1 agent pembrolizumab, the anti-TIGIT agent vibostolimab and the oncolytic virus gebasaxturev, neoadjuvant pembrolizumab-based regimens elicited encouraging clinical responses in patients with resectable melanoma.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Genome-wide association meta-analyses among 1.4 million individuals identify 318 new risk loci for type 2 diabetes and provide insight into the contribution of these risk variants to diabetes-related vascular outcomes.

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.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Transcription elongation (TE) is a key point of inducible gene expression regulation. Here, the authors report widespread TE defects (TE^deff) in a high proportion of cancers that correlate with poor immunotherapy response, highlighting TE defects as potential routes for immune resistance.

This study shows that among healthy adults tracked across their lives, brain atrophy rates correlate with genetic risk for Alzheimer’s and memory decline, and that degeneration in Alzheimer’s-vulnerable brain regions is a continuous phenomenon.

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.

A genome-wide association study using electronic health record data in the Million Veteran Program uncovers new genetic loci associated specifically with peripheral artery disease, as compared to stroke or coronary artery disease.

Trans-ancestry genome-wide analyses identify multiple loci associated with ascending aortic diameter. A polygenic score constructed from these loci predicted prevalent risk of thoracic aortic aneurysm in independent populations.

Site-specific hyperphosphorylations of tau in the cerebrospinal fluid change with disease course, and correlate with pathology and cognitive decline in dominantly inherited Alzheimer’s disease.

Many aspects of the CD8⁺ T lymphocyte response are 'programmed' by inductive stimuli during primary activation. A recent Nature paper shows that interleukin 2 signals endow CD8 T cells with the capacity for secondary population expansion during priming.

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.