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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

During visual learning, neural plasticity is driven by unsupervised learning in mice.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Insight into the algorithmic form and learning principles underlying cognitive maps in the hippocampus is provided.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

Immunotherapy with immune checkpoint inhibitors and targeted therapy with BRAF and MEK inhibition have revolutionized the treatment of melanoma. Here the authors report the results of a phase II trial of neoadjuvant cobimetinib (MEK inhibitor) and atezolizumab (anti-PD-L1) with or without the BRAF inhibitor vemurafenib in patients with resectable Stage III melanoma.

A two-photon computed tomography approach, called scanned line angular projection microscopy, enables high-speed imaging at over 1 kHz frame rates, as demonstrated for glutamate imaging in the in vivo mouse brain.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

Naomi Wray and colleagues report an analysis of genome-wide association data sets from the Psychiatric Genomics Consortium for five psychiatric disorders. They find that common variation explains 17–29% of the variance in liability and provide further support for a shared genetic etiology for these related psychiatric disorders.

The Psychiatric GWAS Consortium Bipolar Disorder Working Group reports a large-scale genome-wide association study of 7,481 individuals with bipolar disorder with replication in 4,493 cases. The Consortium identifies a new susceptibility locus near ODZ4 and replicates a known association near CACNA1C for bipolar disorder.

Imaging of activity in long-range axons is reported in mice performing tactile object-localization with their whiskers; the feedback projection from the motor cortex to the somatosensory cortex provides information to integrate whisker movement information and touch, which are key components of object identification.

Simone de Jong et al. examine the balance of common and rare risk for psychiatric disorders in a large family with high incidence of Bipolar Disorder and Major Depressive Disorder. They find that increased polygenic risk over generations could be partially due to assortative mating, which may explain the observation of anticipation in mood disorders.