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Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

This study maps chromatin accessibility in neurons and glia in schizophrenia, revealing fetal-like regulatory patterns in adult neurons enriched for genetic risk variants, linking early brain development to schizophrenia pathogenesis

Here the authors provide a comprehensive transcriptomic dataset of human primary microglia for Alzheimer’s disease and healthy aging. They identify dysregulation of immune-related microglial functions as a hallmark of disease.

Transcriptomic and epigenomic profiling of human microglia identifies putative gene regulatory mechanisms for 21 Alzheimer’s disease (AD) risk loci. SPI1/PU.1 is nominated as a key regulator of microglia gene expression and AD risk.

Analysing >1,700 inventory plots from the Amazon Tree Diversity Network, the authors show that the majority of Amazon tree species can occupy floodplains and that patterns of species turnover are closely linked to regional flood patterns.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Induced pluripotent stem cell (hiPSC)-based models have inherent variations in their cellular and molecular output and readouts. Here, Hoffman and colleagues devise a method to account for gene expression variations in hiPSC-derived neurons from patients with childhood-onset schizophrenia.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Transcriptome and functional studies in human iPSC-derived neurons suggest that the phenotypic effects of NRXN1 deletions can occur through reduction in wild-type NRXN1α isoform levels and expression of mutant NRXN1α isoforms.

Voloudakis and colleagues find statistically significant but weak associations between professional categories and genetic predisposition for neuropsychiatric traits.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Brain gene regulation is key for neuropsychiatric disorders. Here, the authors show that profiling gene expression and chromatin states in 25 brain regions enables enhancer-promoter mapping at isoform resolution, improving genetic fine-mapping.

Genome-wide association studies have identified genetic modifiers, mostly DNA repair genes, that significantly influence the onset and progression of Huntington disease, pointing to somatic CAG repeat expansions as a key pathological driver. Here, Tabrizi and colleagues review the evidence for this paradigm and discuss the potential for therapeutic interventions.

Simultaneous profiling of RNA and chromatin accessibility in single nuclei isolated from human postnatal brain regions from infancy to late adulthood identifies key cellular regulators and nominates target genes and mechanisms for brain-related diseases and disorders.

Chemical proteomics identified covalent ligands targeting an isoform-restricted allosteric cysteine in JAK1. The compounds inhibit JAK1-dependent signaling in immune cells with unprecedented selectivity.

A multi-ancestry expression quantitative trait locus meta-analysis of 3,983 RNA-seq samples from 2,119 donors using the multivariate multiple QTL (mmQTL) approach characterizes the genetics of gene expression in the human brain and identifies candidate causal variants for brain-related traits.

This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and novel isoforms in 555 samples from 391 donors finds associations with genetic risk loci in Alzheimer’s and Parkinson’s diseases.

SEAMLESSM4T is a single machine translation tool that supports speech-to-speech translation, speech-to-text translation, text-to-speech translation, text-to-text translation and automatic speech recognition between up to 100 languages.

This study analyzes allelic expression bias in post-mortem brains of healthy individuals and those diagnosed with schizophrenia or bipolar disorder. The study shows that the number of imprinted genes is consistent with low estimates, and that allelic bias is independent of psychiatric disease status.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

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.

Breen et al. map RNA editing profiles in cortical samples from individuals with schizophrenia and controls, and find links between altered RNA editing in glutamatergic and postsynaptic density genes and schizophrenia genetic risk architecture.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

Analyses of population-level variation in gene and enhancer expression in the human brain characterize the gene–enhancer regulome and the regulatory mechanisms of transcribed enhancers in neuropsychiatric diseases.

Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.

This PsychENCODE resource presents 157 reference maps for open-chromatin-associated histone methylation and acetylation in prefrontal and anterior cingulate cortex, linking the neuronal epigenome to the genetic risk architecture of schizophrenia.

Girdhar et al. constructed chromosomal domains from prefrontal histone acetylation and methylation maps and discovered, in a large cohort of schizophrenia and bipolar brains, converging alignment by genetic risk, neuronal function and three-dimensional genomics.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Genome-wide association analysis of a binge eating disorder phenotype derived from a supervised machine-learning model applied to electronic medical records identifies three risk loci for this disorder and implicates iron metabolism in its etiology.

Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

Cross-disorder genetic association analyses identify five loci differentiating attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Individuals diagnosed with both ADHD and ASD are double-loaded with genetic risk for both disorders.

The protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccine expressing the SARS-CoV-2 spike protein in non-human primates is demonstrated.

Tree species turnover across Amazonian forests unveils sharp floristic transitional zones, that are linked with changes in soil fertility and climate.

PrediXcan is a widely used gene expression imputation method that links genetic variants to gene expression. Here, the authors develop EpiXcan which leverages epigenetic annotations to inform transcriptomic imputation and further use the obtained gene-trait associations for computational drug repurposing.

In this study, the authors develop a comprehensive taxonomy of brain-wide SPNs, identifying several novel subsets via their transcriptional signatures.

Increasing zonal asymmetry in tropical precipitation is projected by 2100, with increases over Asian and African forests and decreases over South American forests. Plant physiological responses to increasing CO₂ are now identified as a primary driving mechanism.