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Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

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.

RBM7 and ZCCHC8 are two core subunits of the Nuclear Exosome Targeting complex, which regulates the degradation of selected non-coding RNAs in human cells. Here, the authors use structural and biochemical methods to show how ZCCHC8 recruits RBM7 in the complex, leaving the RNA binding site accessible and revealing possible implications for splicing.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Inducible nitric oxide (NO) synthase (iNOS) is essential in the response to mycobacterial infection, yet NOS signalling can occur through NO-dependent or NO-independent pathways. Here the authors show macrophage Gch1 and tetrahydrobiopterin mediate NO-independent control of Mycobacterial infection.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

Climate change is expected to have major impacts on forest tree diseases. Here the authors analyse long-term data of white pine blister rust in the southern Sierra Nevada, finding evidence of climate change-driven disease range expansion that was mediated by spatially varying host-pathogen-drought interactions.

Chromothripsis and chromoanasynthesis lead to locally clustered rearrangements affecting one or a few chromosomes, but their impact on cancer development and progression is unclear. Here the authors analyse the role of DNA repair factors in brain tumors by whole-genome sequencing of tumors from mouse models of medulloblastoma or high grade gliomas.

The transcription factor PU.1 is an essential regulator of the pro-fibrotic gene expression program in fibroblasts; PU.1 expression is upregulated in various fibrotic diseases, whereas inactivation of PU.1 induces regression of fibrosis in a number of organs.

Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

The size of the inner disk of the T Tauri star TW Hydrae is determined using optical long-baseline interferometric observations, indicating that hydrogen emission comes from a region approximately 3.5 stellar radii across.

Virtual photons emitted from strong-interaction matter created in relativistic heavy-ion collisions decay into electron–positron pairs, which provide information about the system’s properties.

Population-based genome sequencing provides an increasingly rich resource for the identification of low-frequency, large effect variants associated with clinically important phenotypes. Timpson et al. use UK10K data to identify a variant of the APOC3gene strongly associated with plasma triglyceride levels.

Severe congenital development defects such as Jeune syndrome can result from the malfunction of primary cilia and dynein. Here Schmidts et al. report unique biallelic null mutations in a gene encoding a dynein light chain, helping to explain the nature of ciliopathies in human patients.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

Answer ALS is a resource of patient-derived iPS cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This serves as a foundation to identify distinct disease subgroups.

The coordinated action of BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX) regulates auxin flux during the development of protophloem sieve elements in the root meristem of Arabidopsis.

This Review discusses the emerging concept that resistance to the metabolic adverse effects of lifestyle factors is mediated by an adaptive response to cellular stress, counteracting mechanisms that otherwise lead to impaired insulin signaling and β cell failure. This response exhibits characteristics of hormesis, originally described in toxicology, whereby exposure of cells, tissues or organisms to low levels of toxin induces resistance to higher toxin concentrations.

Risk stratification based on plasma p-tau217 can substantially reduce the need for invasive or expensive testing when screening for Aβ positivity in patients with cognitive impairment, offering a cost-effective strategy to support an Alzheimer’s disease diagnosis.

GPCRmd is a community-driven online platform to visualize, analyze and share G-protein-coupled receptor (GPCR) molecular dynamics data. It currently contains simulation data representing 100% of GPCR classes, 71% of receptor subtypes and 80% of GPCR families.

An aromatic hydrogen bond—an interaction between the π-electron cloud of an aromatic ring and a hydrogen-bond donor—can substitute for a conventional hydrogen bond in sequence-specific protein—DNA interactions and can contribute 0.5–1 kcal mol⁻¹ to binding and 1–2 kcal mol⁻¹ to specificity.

Adoptive cell therapy (ACT), using either autologous tumour-infiltrating lymphocytes or donor lymphocytes, has proved an effective treatment for some patients with advanced cancers. Can the ability to genetically engineer human lymphocytes for ACT further expand the use of this treatment?

Current theories of addiction all argue for a unitary account of drug addiction. Badiani and colleagues challenge this view by highlighting behavioural, cognitive and neurobiological differences between opiate addiction and psychostimulant addiction. They argue that these differences have important implications for addiction treatment, addiction theories and future research.