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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.

Head-on collision between the replication and transcription machineries halts DNA synthesis. This work examines what happens when a replisome bumps up against an engaged RNA polymerase. The study finds that the RNA polymerase is displaced from the DNA, but the replisome and the nascent mRNA remain attached. A replication assembly factor, the β-clamp, finds the 3′ end of the mRNA and recruits the still-bound replisome, which exploits the mRNA as a primer to reinitiate DNA synthesis.

During chromosome replication, coupled polymerases introduce topological changes that cause lower processivity and transient lagging-strand polymerase dissociation from DNA.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

Here, the authors compared measurements between 34 laboratories from 19 countries, to quantify by mass spectrometry four ceramides of clinical relevance in human blood plasma Standard Reference Materials. The main goals were to evaluate concordance obtained in a large inter-laboratory trial and to report absolute concentrations of four circulating lipids in a publicly available standard.

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.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Processive DNA polymerases that replicate chromosomes interact with a ring-shaped clamp that encircles DNA and slides along the duplex. The sliding clamp is loaded onto DNA by a clamp-loader complex. Structural and biochemical studies have provided mechanistic insights into the clamp-loading process.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Eukaryotic DNA replication is carried out by two DNA polymerases, Pol ɛ and Pol δ. An in vitro–replication system reconstituted with purified yeast components identifies the factors that selectively recruit each polymerase for leading- or lagging-strand synthesis.

Recent work has indicated that the Escherichia coli replisome contains three DNA polymerases that are used to replicate two parental strands. A single-molecule approach is now used to compare replisomes reconstituted with two or three polymerases, revealing that the presence of a third polymerase ensures higher processivity overall and more efficient replication of the lagging strand.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

Genetic evidence has implicated the SOS-induced translesion DNA polymerase DinB (Pol IV) in error-prone recombination. Now biochemical analyses show that Pol IV outcompetes high-fidelity polymerases during the extension of D-loop recombination intermediates under SOS response conditions, providing new insight into the mechanism of stress-induced mutations in Escherichia coli.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Nathan Pankratz, Santhi Ganesh and colleagues use exome chip data to identify rare and common variants influencing blood cell traits. They report associations at several loci, including a rare missense variant in S1PR4 associated with circulating neutrophil counts, and present functional studies supporting a role for S1PR4 in neutrophil recruitment and resolution in response to tissue injury.

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.

Replication initiators in both bacteria and eukaryotes are AAA+ proteins that bind and remodel origin DNA sequences, preparing them for chromosome duplication. Two new reports show that the bacterial DnaA and eukaryotic ORC initiators form protein helical filaments. Wrapping of origin DNA around these filaments may promote DNA unwinding and subsequent assembly of replication forks.

The largest meta-analysis of GWASs of hepcidin and sTfR identified 43 genomic loci, of which 15 new. Mendelian randomisation revealed associations of systemic iron status and iron-related loci with selected health outcomes across multiple domains.