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Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Schneeberger, Kim, Geesdorf, Rajewsky, Heppner et al. tease IL-12 and IL-23 signaling apart in mouse models and human brain tissue to define a role for oligodendroglial and neuronal IL-12 signaling in neuroimmune crosstalk in Alzheimer’s disease.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Molecular Pixelation is an optics-free method that uses DNA-tagged antibodies to enable identification of the relative location of proteins on single cells.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

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.

Pigs are important large animal models for biomedical research. Here, the authors construct a single-cell landscape of pig tissues, unravelling the phenotypic heterogeneity of blood endothelial cells in adipose tissues and the evolutionally conserved regulons of microglia in brains.

Climate warming causes riverine CO₂ emissions increasing at 0.42 ± 0.16 Tg C yr⁻¹ in the Northern Hemisphere permafrost regions during 2000–2020.

In a biomarker-driven, outcome-adaptive platform trial for patients with metastatic castration-resistant prostate cancer, androgen receptor pathway inhibitors showed longer survival with respect to taxanes and physician’s choice treatment.

This study offers molecular insight into the sialidase and fucosidase decapping apparatus that initiates growth on mucin and promotes nutrient sharing by the dedicated mucolytic symbiont Akkermansia muciniphila with the mucus-associated microbiota.

This genome-wide association study identifies 162 genetic loci linked to income, shedding light on the complex interplay between genetics, income, education and health.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Men develop larger myocardial infarction (MI) sizes than women. Here, the authors show that male sex and testosterone, via bone marrow stroma, exacerbates MI-induced neutrophilia and cardiac injury and that response to anti-inflammatory treatment in MI is greater in men than women

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

Rivers and lakes are thought to be a major conduit of loss for the massive amounts of carbon locked away in high-latitude systems, but such losses are poorly constrained. Here the authors quantify carbon emissions from rivers and lakes across Western Siberia, finding that emissions are high and exceed carbon export to the Arctic Ocean.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

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.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe.

Cancer cells often acquire molecular patterns of fast-growing embryonic tissues to enable propagation and invasion, which distinguish tumour tissues from their healthy adult counterpart. Here authors develop antibody fragments which specifically target oncofetal chondroitin sulphate on the cancer cell surface and in the tumour stroma, with the antibodies achieving therapeutic effect in multiple mouse models in antibody drug conjugate and bispecific immune cell engager formats.

Not accounting for coupled land–water carbon fluxes can lead to flawed understanding and incorrect assessments of climate impact and feedback on the Arctic carbon cycle. There is a need for collaborative studies, between scientific disciplines and approaches, that integrate carbon transformations and fluxes across the Arctic land–water continuum.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships.

Lake ecosystem productivity, defined by the rate of biomass synthesis, is believed to be limited by nutrient availability. However, the comparison of several small unproductive lakes along a water colour gradient now shows that coloured terrestrial organic matter controls the key process for new biomass synthesis through its effects on light attenuation, suggesting that light is the more important limiting factor.

The Western Siberia Lowland (WSL) is the world’s largest frozen peatland complex, however carbon emissions (CO₂+CH₄) from lakes in this region remain unknown. Here, the authors sample 76 lakes and show high carbon emissions from lakes across all permafrost zones in the WSL.

Rivers in the Western Siberian Lowland, the world’s largest peatland, play a significant role in the release of terrestrial carbon to the atmosphere, according to in situ measurements of carbon dioxide emissions from rivers.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

CH₄ inputs to Arctic lakes via groundwater discharge are an important pathway that links CH₄ production in thawing permafrost to emission via lakes. Here the authors unravel the role and drivers of groundwater inflows for CH₄ emissions from Arctic lakes.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Common polygenic variation at chromosome 16p and rare recurrent deletions of 16p11.2 influencing autism risk are associated with reduced expression of genes throughout the 16p region, suggesting functional convergence of rare and common variant effects.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

While mycorrhizal-plant interactions are widely studied, other root symbionts may also be ecologically important. Here, the authors show that dark septate endophytes are a strong predictor of rhizosphere and associated soil microbiomes in broad-leaved tree across Europe.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

The ordered display of antigen patterns on DNA origami platforms combined with surface plasmon resonance chips allows the investigation of the affinity and kinetics of the antigen–antibody bivalent binding in relation to the antigen distance and antibody flexibility.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.