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Genetic models for psychiatric disorders often overlook ancestry diversity. Here, the authors use PsychENCODE and GWAS data to build ancestry-specific GReX models, improving TWAS and revealing novel genes and pathways linked to brain development and psychiatric risk.

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 authors develop a supervised and unsupervised learning algorithm Signature. Machine learning and network model analysis of Hi-C datasets across 62 2n genomes suggest that inter-chromosomal contacts demarcate genome topology along a spatial gradient of genome activity.

A subset of pediatric gliomas harbour alterations in fibroblast growth factor receptor (FGFR)-family proteins. Here, the authors characterise the genomic landscape of 11,635 gliomas across ages and use isogenic model systems to explore the underlying biology of FGFR1-altered gliomas and potential therapeutic vulnerabilities.

Histone H3-mutant gliomas are deadly brain tumours and the tumour microenvironment is not fully understood. Here the authors profile the immune microenvironment from human samples and mouse models and implicate myeloid cells in immune suppression and show inhibition of myeloid cells and checkpoint blockade demonstrates therapeutic benefits in mice.

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.

SpaceX’s Inspiration4 mission sent an all-civilian crew into orbit to study physiological, neurovestibular and neurocognitive changes in the astronauts and found that short-duration civilian space missions do not pose a major health risk.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

A single-cell transcriptomic atlas from embryonal pons and forebrain provides insights into the developmental origins of pediatric brain tumors. The study identifies impaired differentiation of specific neural progenitors as a common mechanism underlying these cancers.

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

Agnihotri and colleagues show that loss of the MAT2A enzyme of the methionine cycle induces a global depletion of H3K36me3 and extends survival in glioma models, representing a potential therapeutic vulnerability.

Here the authors provide the biospecimen collection methodology from the SpaceX Inspiration4 mission, including venous blood, capillary blood, saliva, urine, stool, skin biopsy, body swab, and environmental swab samples.

Here, the authors report that schizophrenia risk variants mapping to a striatal dopamine-related gene set are associated with increased striatal dopamine synthesis capacity and increased striatal activity during reward anticipation in humans.

Multiple omics platforms and deep single-cell profiling in the I4 astronauts reveal both conserved and distinct immune system disruptions across missions, provide a single-cell immune reference for future missions.

Sequencing data from the developing cerebellum are compared with bulk sequencing data from paediatric tumours, providing insights into their potential origins and suggesting that many cerebellar tumours have their origins early in utero.

Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.

Analysis of large genomic datasets, including gnomAD, reveals that partial LRRK2 loss of function is not strongly associated with diseases, serving as an example of how human genetics can be leveraged for target validation in drug discovery.

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.

Complex I inhibition induces oxidative stress leading to cancer cell cytotoxicity. Here, the authors show, in breast cancer models, that inflammatory mediators can potentiate complex I inhibitor phenformin cytotoxicity through STAT1-mediated downregulation of the reactive oxygen species scavenger NQO1.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

A multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Getting cultured cells to 'do their job'—either to recreate in vivo function in an artificial setting or to churn out immense volumes of protein on command—requires both an understanding of the demands of cell physiology and the technology to meet those demands. Michael Eisenstein looks at contemporary solutions for culture conundrums.

A comprehensive analysis of brain somatic mosaicism across the neocortex demonstrates the origins and distribution patterns of cells within the human brain.

Genome-wide association analyses identify 301 new loci influencing bone mineral density and 13 loci influencing fracture risk. Integrative analyses of epigenomic data and mouse knockout phenotypes provide additional insights into osteoporosis pathophysiology.

Elevated levels of interleukin-33 have been associated with poor prognosis in patients with glioma. Here the authors show that glioma-derived IL-33 modulates a pro-tumorigenic immune microenvironment by activating resident and recruiting peripheral innate immune cells.