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Exome sequencing analysis of 13,933 individuals with bipolar disorder finds enrichment of ultra-rare protein-truncating variants in constrained genes. Combined analysis with schizophrenia exome data identifies AKAP11 as a risk gene for both disorders.

The mechanisms underlying epilepsy development are not well understood. Here the authors show that loss of a key component of the so called blood-brain barrier drives seizures in mice and is also lost in humans with treatment resistant epilepsy

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Genome-wide analyses for 7,266 traits leveraging data from several genetic ancestry groups in UK Biobank identify new associations and enhance resources for interpreting risk variants across diverse populations.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Equitable and accessible education in life sciences, bioengineering, and synthetic biology is crucial for training the next generation of scientists. Here the authors present the CRISPRkit, a cost-effective educational tool that enables high school students to perform CRISPR experiments affordably and safely without prior experience, using smartphone-based quantification and an automated algorithm for data analysis.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

WebSchizophrenia is associated with genetic variation at the major histocompatibility complex locus; this study reveals that alleles at this locus associate with schizophrenia in proportion to their tendency to generate greater expression of complement component 4 (C4A) genes and that C4 promotes the elimination of synpases.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Adoptive T-cell immunotherapy offers promise to patients who are resistant to standard anti-viral strategies. Here the authors describe clinical observations in patients with viral complications treated with adoptive immunotherapy over the last 15 years.

How the 22q11.2 deletion predisposes to psychiatric disease is unclear. Here, the authors examine living human neuronal cells and show that 22q11.2 regulates the expression of genes linked to autism during early development, and genes linked to schizophrenia and synaptic biology in neurons.

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.

Patrick Sullivan and colleagues report a multi-stage genome-wide association study for schizophrenia in a Swedish population. They identify 13 loci newly associated with schizophrenia.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Whole-exome sequencing identifies ten risk genes for schizophrenia implicated by rare protein-coding variants, a subset of which overlap with risk genes in other neurodevelopmental disorders.

Inversion of the mouse α-globin super-enhancer reverses expression and interaction profiles of flanking genes. Contrary to the orientation-independent paradigm of enhancers, this super-enhancer acts in an orientation-dependent manner.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

Characterization of the genomes of the parasite Onchocerca volvulus, the causative agent of river blindness, and its Wolbachia symbiont reveals potential therapeutic targets.

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.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Genetic variants on chromosome 8q24 are associated with prostate cancer risk in men of African ancestry. Here the authors show that one of these variants, rs72725854 alters the enhancer activity in its region, which upon androgen stimulation, activates multiple oncogenic lncRNAs and c-myc.

Enteric Yersinia pseudotuberculosis infection is contained by host inflammatory monocyte-driven pyogranuloma formation to counter bacterial YopH-dependent anti-neutrophil activity.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

The magnetic field measured by the InSight lander on Mars varies daily and is ten times stronger than expected. The field is inferred to originate from components of basement rocks magnetized by an ancient dynamo of Earth-like strength.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Function-altering variants of immune-related genes cause rare autoimmune syndromes, whereas their contribution to common autoimmune diseases remains uncharacterized. Here the authors show that rare variants of lupus-associated genes are present in the majority of lupus patients and healthy controls, but only the variants found in lupus patients alter gene function.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Opioid use disorder (OUD) is influenced by genetic and environmental factors. Here, authors use a multi-omics approach to reveal DNA hydroxymethylation as an important gene regulatory mechanism for OUD in the human brain.

Prospective assessment of a T-cell-inflamed gene signature and tumor mutational burden is feasible in patients with non-small cell lung cancer randomized to receive various anti-PD-1-based treatment combinations, with an encouraging objective response rate for first-line pembrolizumab + lenvatinib in one biomarker-defined group.

Characterizing how genetic variation impacts cell morphology can provide an important links between disease association and cellular function. Here the authors identified the morphological impacts of genomic variants by generating high-throughput morphological profiling and whole genome sequencing data on iPSCs from 297 donors.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Taisei Kikuchi, Mark Viney, Matthew Berriman and colleagues report the genome sequences of six species of nematodes from the Strongyloides clade of nematodes, including human and animal pathogens, facultative parasites and a free-living species. They find that expansions of the astacin and SCP/TAPS gene families are associated with parasitism in these species.

Using multiple datasets from real-world evidence and completed trials, a machine learning model using routine blood and clinical data is shown to be predictive of patient response to immune checkpoint inhibitor therapy, across cancer types and outperforming standard biomarkers.

Anti-CRISPR proteins derived from phage can abrogate CRISPR activity. The authors repurpose these molecules for demonstrating genomic write-protection and pre-programmed gene expression circuits.

A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.