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Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Hepatic stellate cells regulate hepatocyte functions via R-spondin 3.

Xu et al. show that liver ATF3 expression is inhibited by hydrocortisone, thus promoting the development of atherosclerosis through effects on HDL cholesterol and bile acid metabolism.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Experimental systems in which non-trivial topology is driven by spontaneous symmetry breaking are rare. Now, topological gaps resulting from two excitonic condensates have been demonstrated in a three-dimensional material.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Using ribosome profiling, Navickas et al. show that heterogeneous nuclear ribonucleoprotein C functions with PABPC4 to regulate alternative polyadenylation of a set of mRNAs, which inhibits lung metastasis in xenograft models of breast cancer.

Immunotherapy resistance is common among melanoma patients. Here, the authors identify three resistance mechanism subtypes across tumor-derived cell lines and matched samples and highlight antigen presentation disruption as a key mediator of resistance.

Subpopulations of cytokine-producing and myofibroblastic hepatic stellate cells, identified by single-cell RNA sequencing, protect against or promote the development of hepatocellular carcinoma via high expression of hepatocyte growth factor or type I collagen, respectively..

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

The cis-regulatory functions of human accelerated regions of genomic loci and their potential contribution to human brain evolution are revealed.

Disentangling causal interactions among biodiversity, ecosystem functioning and environmental factors is key to understanding how ecosystems respond to changing environment. This study presents a global scale analysis quantifying causal interactions and feedbacks among phytoplankton diversity, biomass and nutrients along environmental gradients of aquatic ecosystems.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Somatic copy number alterations (CNAs) of parts of the genome can contribute to the development and progression of various cancers. Here, the authors present a statistical method to detect clonal and allele-specific CNAs from single-cell RNA-sequencing data with high robustness.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

In recent history the amount of carbon captured by terrestrial systems has increased, but the processes driving this process has remained poorly constrained. Here the authors use a global carbon model to show that a decrease in wildfires has caused the land carbon sink to increase in the past few decades.

Andrew Futreal and colleagues report inactivating somatic mutations in the histone lysine demethylase gene UTX in human cancers, including multiple myelomas, esophageal squamous carcinomas, renal clear cell carcinomas, acute and chronic myeloid leukemias, breast and colorectal cancers and glioblastomas, identifying UTX as a new tumor suppressor gene.

Genetic fine-mapping and CRISPRi screens identify functional variants and their target genes associated with Alzheimer’s disease in microglia. The variant rs7922621 modulates AD risk through control of TSPAN14 expression in this cell type.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Duan et al. show that ACE2-dependent and ACE2-independent entry of SARS-COV-2 in epithelial cells versus myeloid cells differentially regulates viral replication and inflammatory responses, thereby contributing to COVID-19 progression and pathology.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

It is unclear whether somatic mutation rates are elevated in Lynch Syndrome (LS), which is the most common cause of hereditary colorectal cancer. Here, the authors use whole-genome sequencing and organoid cultures to show that normal tissues in LS patients are genomically stable, while ancestor cells of neoplastic tissues undergo multiple cycles of clonal evolution.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Pseudovirus assays and surface plasmon resonance show that the Omicron receptor-binding domain binds to human ACE2 with increased affinity relative to the ancestral virus, and that most neutralizing antibodies are considerably less potent against Omicron.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Zhang et al. have data suggesting that, in the chicken embryo, monocytes foster a pro-angiogenic microenvironment in advance of angiogenesis by depositing migrasomes enriched in angiogenic factors.

A significant proportion of patients develop innate or acquired resistance to immune checkpoint inhibitors. Here, the authors show that resistance to anti-PD-1 blockade is associated with TGF-beta driven major histocompatibility complex I (MHCI) down-regulation and a de-differentiated phenotype in melanoma patients.