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Comparisons of phenotypic and genetic association with protein levels from Icelandic and UK Biobank cohorts show that using multiple analysis platforms and stratifying populations by ancestry improves the detection of associations and allows the refinement of their location within the genome.

A genome-wide association study of plasma protein levels measured with 4,907 aptamers in 35,559 Icelanders highlights links with over 370 disease endpoints and other traits.

Understanding the underlying pathophysiology of obesity can help prevent this condition. Here, the authors perform a GWAS of BMI in diverse ancestries, finding four missense variants in FRS3 that affect BMI.

Allele-specific DNA methylation data in whole blood from 7,179 individuals sequenced by Nanopore, and gene expression profiles from 896 samples, show that DNA sequence variability accounts for most of the correlation between CpG methylation and gene expression.

Large-volume volcanic eruptions can occur despite only limited precursory activity. Here the authors show that modelling the combined effects of buoyant magma, viscoelastic earth behaviour, and sustained magma channels can explain such behaviour of volcanoes and gives an estimate of pressure evolution in magma bodies.

Application of a nanopore sequencing workflow for real-time analysis of brain tumors results in molecular classification within a 30-minute intraoperative window, followed by comprehensive profiling within 24 hours.

Burden testing in three large European ancestry cohorts identifies new risk genes for a number of common cancer types, including pan-cancer protective variants in AURKB and breast cancer protective variants in PPP1R15A.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

To measure selection on variants, whole-genome sequencing of approximately 150,000 individuals from the UK Biobank is used to rank sequence variants by their level of depletion.

A barcode-based approach applied to UK Biobank and an Icelandic cohort identifies drivers of clonal hematopoiesis (CH) and finds associations between CH and multiple diseases. Genome-wide association analyses identify 25 loci associated with CH susceptibility.

Yuan et al. present crossNN, an explainable machine learning tool to classify tumors based on DNA methylation data from several platforms with different epigenome coverage and sequencing depth, benchmark against other models and validate externally.

Genome-wide analyses identify loci associated with nonalcoholic fatty liver disease, including rare, protective loss-of-function variants in MTARC1 and GPAM. Plasma proteomic analyses provide insight into proteins involved in disease pathogenesis.

MethyLYZR, an epigenetic classifier of brain tumors, provides clinically relevant cancer classification results within 15 min of sequencing, with potential applications for neurosurgical intraoperative use.

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.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Ruth Loos and colleagues use genome-wide association to identify common variants influencing body fat percentage. Unexpectedly, they show that a body-fat–decreasing allele near IRS1 is associated with an impaired metabolic profile, including increased risk of type 2 diabetes and coronary artery disease.

Rare copy-number variants (CNVs) conferring risk of schizophrenia or autism affect fecundity of carriers in Iceland, and carriers of these CNVs who do not suffer disease or have not been diagnosed with intellectual disability show phenotypes in brain structure and cognitive abilities between those of non-carrier controls and patients with schizophrenia.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

The genetics of schizophrenia and other mental disorders are complex and poorly understood, and made even harder to study due to reduced reproduction resulting in negative selection pressure on risk alleles. Two independent large-scale genome wide studies of thousands of patients and controls by two international consortia confirm a previously identified locus, but also reveal novel associations. In this study, de novo (spontaneous) copy number variants are reported on chromosomes 1 and 15.

Ingileif Jonsdottir, Kari Stefansson and colleagues show that variants in the HLA class II region contribute to tuberculosis risk in populations of European ancestry. They propose that the associated variants influence disease risk by altering expression of HLA class II molecules presenting protective M. tuberculosis antigens to T cells.

Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.

Gudmar Thorleifsson and colleagues report a genome-wide association study for kidney stones. They report common variants in CLDN14 associated with increased risk of kidney stone disease.

Evgenia Mikaelsdottir et al. report a study of variants associated with platelet count among European individuals where they identify 577 associations. They also report a genetic overlap between platelet count and human diseases, including myeloproliferative neoplasms, rheumatoid arthritis, and hypertension, as well as a genetic overlap between platelet count and various physiological markers.

A transformer-based method efficiently detects RNA splicing from 45,000-nucleotide sequences by applying hard attention to select splice site candidates, outperforming SpliceAI in identifying splice sites and disease-related variants.

A GWAS in Iceland reveals that variants in inner nuclear membrane proteins are associated with nuclear morphology of granulocytes and band neutrophil fraction.

Gudjon Oskarsson et al. report a genome-wide association study of hemoglobin concentration in more than 680,000 individuals from Iceland and the UK. They identify six novel rare coding variants at the ACO1 locus that associate with either increased or decreased hemoglobin concentration, two of which have large and opposite effects.

Gudjon Oskarsson et al. report the association of a rare variant in the erythropoietin (EPO) receptor gene, EPOR, with serum EPO levels in the Icelandic population. The variant leads to a truncation of EPO-R without an effect on hemoglobin levels, indicating a possible feedback mechanism in the generation of red blood cells.