Search

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

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.

How diffusible signals determine cell fate is a vital and still unresolved developmental biology issue. Using the Drosophilaegg chamber as a model system, here the authors apply novel imaging and mathematical approaches to show that cell differentiation depends on irregular tissue domains that lead to asymmetric distributions of morphogens.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Chronic stress is a risk factor for mood disorders, yet the molecular and circuit mechanisms of stress-induced changes are not well understood. Here, the authors report the role of the transcription factor ΔFosB in driving activity changes in response to stress in glutamatergic neurons in the ventral hippocampus that project to nucleus accumben.

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.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Mosaic chromosomal alterations (mCAs) in peripheral blood leukocytes are associated with an increased risk of malignancy. Here, the authors use genome-wide genotyping array data to investigate the prevalence of mCAs in sub-Saharan African children with versus those without Burkitt lymphoma.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Perinatal infection with Group B Streptococcus (GBS) is associated with preterm birth, neonatal sepsis, and stillbirth. Here, Korir et al. show that gene cadD, encoding a putative metal efflux transporter, is important for metal detoxification, immune evasion and bacterial proliferation in the pregnant host.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Phylogenetic diversity is decoupled from taxon diversity for the Cape Floristic Region of South Africa, a biodiversity hotspot. It turns out that the more species-rich western part of the Cape has lower evolutionary potential than the more neglected eastern part, with important consequences for conservation planning.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

An examination of inclusion assemblages in Hadean zircons from Jack Hills (Western Australia) is presented, which constrain the magmatic formation conditions to about 700 °C and 7 kbars. This result implies a near-surface heat flow about 3–5 times lower than estimates of global Hadean heat flow. As the only site of magmatism on modern Earth that is characterized by heat flow of about one-quarter of the global average is above subduction zones, it is suggested that the magmas from which the Jack Hills Hadean zircons crystallized were formed largely in an underthrust environment, perhaps similar to modern convergent margins.

p53 inactivation is nearly universal in small-cell lung cancer (SCLC), but its tumor suppressive role in this cancer type is poorly understood. Here the authors show that intertumoral heterogeneity in SCLC influences the biological mechanisms of p53-mediated tumor suppression and identify a role for cyclophilins in p53-dependent necrotic cell death.

Ewing sarcoma (EWS) is a rare pediatric bone cancer typically involving the EWSR1-FLI1 fusion. Here the authors perform a genome-wide association study and report three new EWS risk loci that reside near GGAA repeat sequences, and identify candidate genes (RREB1 and KIZ) from eQTL analysis.

The researchers showcase all-crystalline and hybrid mid-infrared supermirrors with the lowest optical losses ever demonstrated in this wavelength range, representing an unprecedented improvement over any existing mirrors made with any production technology.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Asthma is associated with mucus overproduction; however, the immunological consequences of excess mucus remain poorly understood. Here the authors show that formation of airway plugs by mucus promotes airway hypersensitivity, while deletion of mucous component Muc5acablates it independently of inflammation.

Jorge Reis-Filho and colleagues identify recurrent mutations in PRKD1 in 73% of polymorphous low-grade adenocarcinoma, a malignant tumor of the minor salivary glands. The mutations cause activation of the PRKD1 serine-threonine kinase.

Bag2 acts as a nucleotide-exchange factor for Hsp70 and also binds misfolded substrates. Now structural work reveals that Bag2 promotes nucleotide exchange via a mechanism distinct from other Hsp70 nucleotide-exchange factors, and mapping of the binding sites for client peptides suggests how Bag2 assists Hsp70 in processing misfolded proteins.

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

Zinc finger protein transcription factors are developed for the selective silencing of the mutant huntingtin gene in human neurons in vitro and multiple animal models of Huntington’s disease in vivo while preserving expression of the wild-type allele.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

mTOR complex 1 signalling regulates polyamine metabolism and thereby promotes tumorigenesis, through regulation of the stability of a key enzyme, AMD1.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.