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A machine learning approach is used to analyse multi-omics (proteomics, metabolomics and transcriptomics) data, producing genetic scores for more than 17,000 biomolecular traits in human blood, and identifying possible associations with disease.

Here, the authors present a method to build genetically personalised metabolic models across tissues to estimate individualised reaction fluxes. A fluxome-wide association study in UK Biobank identifies fluxes associated with metabolites and coronary artery disease.

Integrative analyses of whole-blood gene expression and splicing QTLs with protein, metabolite and lipid QTLs from the same individuals shed light on the shared genetic architecture of molecular traits and health outcomes.

A new study combines MRI data with proteomic, metabolomic and RNA data to develop and examine seven organ-specific MRI-based aging clocks, uncovering links to overall mortality and organ-specific diseases.

Aging affects multiple organs and tracking these changes could improve our understanding of disease risk. Here, the authors show that metabolomics-based organ-specific aging clocks can predict future risk of cardiometabolic disease and mortality.

Results of an early-phase breast cancer prevention trial demonstrate the potential for breast cancer prevention in premenopausal women with anti-progestin therapy by inducing epithelial–stromal remodelling and suppression of luminal progenitors.

Whilst superlattices containing thin films of 5d transition metal oxides are expected to yield strong interfacial coupling, only weak effects have been observed. Here, the authors report strong coupling between 3d SrMnO₃ and 5d SrIrO₃due to the interplay of strong Coulomb and spin orbit interactions.

A meta-analysis of genome-wide association studies for 233 circulating metabolites from 33 cohorts reveals more than 400 loci and suggests probable causal genes, providing insights into metabolic pathways and disease aetiology.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

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.

Here, the authors expand knowledge of the genetic architecture of age-related cataracts, exploring associated pathways and drug-gene interactions, and clarify the roles of type 1 diabetes and UV exposure in cataract etiology.

Gene-based rare variant aggregation study with the levels of 1,294 plasma and 1,396 urine metabolites from paired specimens of 4,737 participants reveals graded effects of rare, putatively damaging variants on gene function and human traits.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Raheem, Sliz et al. study the serum metabolome and an imaging-based measure of visceral fat in adults and adolescents. The authors find that, independently of BMI, visceral fat quantity is associated with a metabolomic profile similar to those predictive of type 2 diabetes and myocardial infarction.

Aguilar-Ramirez et al. examine cross-sectional associations between adiposity and metabolic traits among Mexican adults. Their findings suggest that higher total and central adiposity relate adversely, whilst higher gluteo-femoral adiposity relates favourably, to numerous metabolic factors relevant to disease risk.

In a longitudinal population-based cohort, Liu et al. demonstrate that integrating polygenic risk scores and the gut microbiome improved prediction, over traditional risk factors, for heart disease, diabetes, Alzheimer disease and prostate cancer.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Typically, quantitative trait loci studies find genetic variants associated with the total quantity of a quantitative trait, but other measures, such as variance, can detect different biology. Here, the authors map variance quantitative trait loci for blood cell traits, finding associations with gene-by-environment interactions and genetically-predicted alcohol use.

Polygenic scores aim to capture genetic risk but may miss nonlinear genetic and environmental interactions. Here, the authors show that neural networks detect limited nonlinearity and do not outperform linear models, highlighting constraints in current deep-learning approaches.

Quality improvement in medicine has largely focused on conditions managed in primary care rather than specialist care. The American Academy of Neurology has introduced process-focused quality metrics for neurologists managing patients with Parkinson disease with the goal of informing evaluation of clinical performance. These metrics might eventually inform pay-for-performance decisions.

Here, the authors leveraged genetic and proteomic information from the UK Biobank and two randomized controlled trials to characterize how polygenic disease risk for T2D and related comorbidities perturbs the plasma proteome and glean therapeutic insights.

Microbes in ancient groundwaters can be very diverse and productive. Some microbes seem to produce oxygen in the dark, which others use to consume the greenhouse gas methane. Their metabolisms are relevant for groundwater health and global change.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

DNA methylation is associated with breast cancer risk. Here the authors measure DNA methylation in the blood of individuals from 25 Australian families with multiple cases of breast cancer but not known mutations associated with breast cancer risk to identify possible heritable methylation markers.

Astrocytes have functions crucial for brain homeostasis, which are disrupted in many neurological disorders, but how these functions are established during astrocyte maturation is largely unknown. Here the authors show transcriptional and chromatin changes underlying astrocyte maturation in mice and identify transcription factors regulating maturation of cultured astrocytes.

Genome-wide and multitrait analyses identify novel loci associated with hypertrophic cardiomyopathy and relevant left ventricular traits. Gene-level burden analyses show that rare truncating SVIL variants are associated with high risk of hypertrophic cardiomyopathy.

Opportunities, challenges and recommended targeted actions to accelerate qualitative data sharing to address complex socio–environmental problems

Surgical ergonomics in urology has been understudied and underemphasized. This Review characterizes the burden of musculoskeletal injury in urologists and focuses on various ergonomic considerations relevant to the urology surgeon.

Avery et al. utilize data from the UK Biobank in a multivariable Mendelian randomization study to evaluate the effects of branched chain amino acids (BCAAs) on human disease. Their findings suggest observational studies of BCAA phenotypic effects are prone to substantial error, potentially misleading efforts to develop novel therapeutics.

The application of polygenic risk scores (PRSs) in clinical practice has advanced but also received criticism. In this Perspective, major psychological and behavioural arguments against PRS applications are assessed.