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Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

Caudal, Tang, et al. use isobaric quantitative protein interaction reporter (iqPIR) technology to compare the mitochondrial protein interactome in healthy and failing murine hearts, providing molecular-level insights into complex mitochondrial remodeling in heart failure.

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.

Mutations in the splicing factor RBM20 cause aggressive Dilated Cardiomyopathy. Here the authors generated RBM20 R636S mutants and knockout in human iPSC-derived cardiomyocytes. Mutant RBM20 showed different target RNA binding, altered splicing and localization to cytoplasmic processing bodies.

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.

Fine-mapping has previously implicated the non-coding single nucleotide polymorphism rs117701653 as a risk variant for rheumatoid arthritis and type 1 diabetes, however its function remained unclear. Here the authors show that this variant decreases binding of the inhibitory factor SMCHD1 to enhance expression of ICOS, promoting development of potentially pathogenic T peripheral helper cells.

Manganese complexes have long been utilized by nature to catalyze the oxygen evolution reaction (OER) but mirroring their efficiency in artificial electrochemical systems has proven difficult. This study centers on alpha-manganese dioxide (α-MnO₂), which closely mimics natural Mn^IV-O-Mn^III-H_xO motifs, presenting a novel method for manipulating proton coupling within the OER process using an external electric field.

Assessing the conservation status of 1,020 European marine fishes reveals half of large (>1.5 m) fishes are threatened with extinction and stock status diverges geographically: almost all Mediterranean stock is overfished, most northern European stock is not.

Here, the authors assess performance and limitations to polygenic risk scores in different race/ethnic groups. They find that polygenic risk score performance improves with diverse training data, and a better understanding of varying genetic backgrounds, social and environmental factors, and gene-environment interactions, is needed to enhance PRS performance for all groups.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

A longitudinal analysis of viral expansion and clearance rates in 60 individuals sampled daily during acute infection reveals high inter-individual variation in infectious virus shedding, which may contribute to superspreading.

While mass spectrometry-based proteomics largely relies on digesting proteins into peptides, there is no equivalent strategy for polysaccharide analysis. Here, the authors develop a chemical approach to break down poly- into oligosaccharides and present a workflow to identify polysaccharides by oligosaccharide fingerprinting.

A method that allows for the detection of mosaic chromosomal alterations from blood whole-genome sequencing data highlights ancestry-specific differences in the distribution of common and rare germline susceptibility variants.

Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

Here the authors establish that ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammals and yeast, they find that growth in large cells is restricted by genome concentration as if it were a limiting nutrient.

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.

The co-administration of insulin and pramlintide stabilized with cucurbit[7]uril-conjugated polyethylene glycol in diabetic pigs improves the mealtime suppression of glucagon over the separate administration of the two hormones.

Linder et al. show how cancer cells reduce proline biosynthesis through P5CS to cope with glutamine starvation.

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.

HER2-low breast cancer has recently emerged as a targetable subset of breast tumors, for which the molecular landscape remains incompletely understood. Here, the authors use genomic data from 1039 patients to unveil and compare the genomic landscape of HER2-low and HER2-0 breast cancer.

A significant proportion of individuals with inherited neuromuscular disease do not receive a genetic diagnosis. Here, the authors establish CCG expansions in the 5’ untranslated region of ABCD3 as a cause of oculopharyngodistal myopathy (OPDM) in individuals of European ancestry and identify increased expression of expansion-containing ABCD3 transcripts as a possible disease mechanism underlying muscle degeneration.

This study presents the assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia; the results shed light on the evolutionary relationship between European and Asian wild boars.

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.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Here, the authors use SNP-seq to screen 87 lupus risk loci for functional non-coding variants. Validation at one locus identified a risk variant through which enhanced Ikaros binding amplifies expression of the interferon / NFκB regulator IKKε.

First-in-human combined intrathalamic and intrathecal gene therapy in two patients with Tay-Sachs disease provides early evidence on the safety and feasibility of the approach.

AMPK regulates cellular energy balance using its γ subunit as an energy sensor of cellular AMP and ADP to ATP ratios. Here, the authors show that γ2 AMPK activation lowers heart rate by reducing the activity of pacemaker cells, whereas loss of γ2 AMPK increases heart rate and prevents the adaptive bradycardia of endurance training in mice.

The European X-ray free-electron laser (EuXFEL) in Hamburg is the first XFEL with a megahertz repetition rate. Here the authors present the 2.9 Å structure of the large membrane protein complex Photosystem I from T. elongatus that was determined at the EuXFEL.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Providing detailed structural descriptions of the ultrafast photochemical events that occur in light-sensitive proteins is key to their understanding. Now, excited-state structures in the reversibly switchable fluorescent protein rsEGFP2 have been solved by time-resolved crystallography using an X-ray laser. These structures enabled the design of a mutant with improved photoswitching quantum yields.

Forest dynamics are monitored at large scales with remote sensing, but individual tree data are necessary for ground-truthing and mechanistic insights. This study on high temporal resolution dendrometer data across Europe reveals that the 2018 heatwave affected tree physiology and growth in unexpected way.

An analysis of transits of planets over starspots on the Sun-like star Kepler-30 shows that the orbits of the three planets are aligned with the stellar equator; this configuration is similar to that of our Solar System, and suggests that high obliquities are confined to systems that experienced disruptive dynamical interactions.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

Cathy Laurie and colleagues detect mosaicism for large chromosomal abnormalities in peripheral blood in a subset of healthy individuals. They show that the frequency of such events increases with age and is associated with elevated risk of developing a subsequent hematological cancer.

In a Hawaiian fountain eruption, rapid gas expansion cools the melt below the glass transition temperature and causes brittle magma fragmentation, producing small, vesicular pyroclasts, according to observations of the 2018 eruption of Kīlauea.

The changes that prostate cancer (PCa) induces in its microenvironment are not fully understood. Here the authors use single-cell RNA-seq and organoids to characterise how the microenvironment responds to PCa, and also identify tumour-associated epithelial cell states and club cells.

In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy.

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.

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.

Whether temporal variations in brain MRI metrics can be attributed to circadian or diurnal oscillations is unclear. Here, the authors show evidence for diurnal oscillations in MRI metrics in both healthy controls and participants with bipolar disorder.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.