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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.

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.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

The authors show that haploinsufficiency of TBK1 causes familial forms of the neurodegenerative diseases ALS and FTD. Loss of binding of a TBK1 protein interaction domain to optineurin, a protein previously linked to ALS, is sufficient to cause the disease. Both proteins regulate autophagy and inflammation.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

HecRE is identified as a molecular switch regulating cyclic di-GMP levels and promoting binary cell states during Pseudomonas aeruginosa surface colonization and biofilm development.

Here the authors identify the transcription factors TFAP2C and TEAD4 as a bistable switch that reconciles into Hippo ON and OFF states, establishing a composite state at the eight-cell stage and critically regulating lineage diversification.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is driven by SMARCA4 loss. Here the authors demonstrate that SCCOHT cells are highly sensitive to CDK4/6 inhibition and provide mechanistic insights, whereby this druggable vulnerability is driven by cyclin D1 deficiency induced by SMARCA4 loss.

Encoding data in DNA is a promising approach to high density data storage. Here the authors present a prototype sequencing-free method that uses the spatial orientation of DNA strands with super-resolution microscopy readout.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Jens Lykke-Andersen, Frank Baas, Joseph Gleeson and colleagues report that mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia type 7. They further show that these mutations result in the accumulation of incompletely processed small nuclear RNAs, leading to severe, early-onset neurodegeneration.

An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

The levels of 1,251 metabolites are measured in 475 phenotyped individuals, and machine-learning algorithms reveal that diet and the microbiome are the determinants with the strongest predictive power for the levels of these metabolites.

Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

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.

A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients.

Synthetic DNA spike-ins that recapitulate genetic variation present in human genomes serve as quantitative and qualitative controls for genome sequencing and variant detection.

Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal chondroitin sulfate, which is expressed by all cancer cells

Synthetic spike-in standards (‘sequins’), representing spliced mRNA isoforms, provide internal controls for assessing transcript assembly and quantification within and between RNA sequencing libraries. Sequins representing fused genes can be used to determine the sensitivity limit for oncogenic fusions in cancer samples.

Examination of the global uranium cycle — whereby uranium from the Earth’s crust is first transported to the oceans and then returned, by subduction, to the mantle — shows that the subducted uranium is isotopically distinct from the Earth as a whole and that this signature has been stirred throughout upper mantle, arguably within the past 600 million years.

A study demonstrating increasing error suppression with larger surface code logical qubits, implemented on a superconducting quantum processor.

Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.

Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

The hippocampus has an undisputed role in memory and has been key in discovering synaptic plasticity as the basis for learning. Bliss and colleagues provide an update on unresolved problems that surround LTP and memory, and propose strategies for finding answers that centre on new technologies.

Jan Veldink and colleagues show that loss-of-function variants in NEK1 are associated with susceptibility to amyotrophic lateral sclerosis (ALS). In addition to finding an excess of rare loss-of-function NEK1 variants in ALS cases, they report a significant association between a specific NEK1 missense variant (p.Arg261His) and disease risk.

Rumen microbiome biology gets a boost with the release of 410 high-quality reference genomes from the Hungate1000 project.

In this Consensus Statement, the Treatment Response Measure for Systemic Lupus Erythematosus Consortium presents the initial outcomes of a project to develop a clinical outcome assessment that can contribute to the regulatory approval process for therapeutic agents via its incorporation in end points of clinical trials in systemic lupus erythematosus.

Evidence suggests that activity in the anterior cingulate cortex (ACC) contributes to acute and chronic pain. In this article, Zhuo and colleagues review the different types of synaptic plasticity observed in the ACC and the implications of these forms of plasticity for pain processing.

John Rioux, Andre Franke, Tom Karlsen and colleagues perform a fine-mapping study of the HLA region in Crohn's disease and ulcerative colitis. They identify a primary role for HLA-DRB1*01:03 in both diseases and find evidence of heterozygous advantage in protection against ulcerative colitis.

Innovative partnerships among researchers, patients, regulators, payors and industry are needed to reinvigorate drug discovery for central nervous system disorders. Here, representatives of the 2013 Collegium Internationale Neuro-Psychopharmacologicum (CINP) Summit group summarize plans to achieve this goal.