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Studies have found that one of the most widely used illicit drugs, marijuana, could hold great therapeutic promise for the treatment of obesity, dyslipidemia, insulin resistance and atherosclerosis. Paul Szmitko and Subodh Verma discuss how modulation of the endocannabinoid system might form the basis of new therapeutic strategies for these pathophysiologically linked conditions.

Marijuana smoke can have harmful effects on the heart. But one of its active components may ease inflammation and slow the progression of coronary artery disease.

Using various mouse models, human plaque data and isolated B cells combined with state-of-the-art imaging and transcriptomic analysis, the authors show that the G-protein-coupled orphan receptor GPR55 regulates B cell activation and plasma cell differentiation during hypercholesterolemia, which crucially affects atherosclerosis.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

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.

Elisabeth Mangold and colleagues report a genome-wide association study for non-syndromic cleft lip with or without cleft palate.

Observation of glioblastoma invasion in subcortical brain regions is challenging. Here the authors develop a Deep3P workflow to enable longitudinal deep imaging of glioblastoma and its microenvironment by combining three-photon microscopy and deep learning-based analysis, unraveling the invasion routes of these tumor cells into and within the white matter.

Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.

Elisabeth Mangold and colleagues carried out a genome-wide association study for nonsyndromic cleft lip with or without cleft palate, and report a locus on 8q24.21 that is strongly associated with this phenotype.

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.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.

Activation of caged fluorophores has mostly relied on the absorption of either a single ultraviolet photon or two NIR photons. Here, the authors show that two green photons (515 nm) can substitute for a single photon ( ~ 260 nm) to activate rhodamine-based dyes, thus enabling STED imaging in thick samples.

Axel Hillmer and colleagues present a genome-wide association study for male-pattern baldness. They confirm a previous association with the gene encoding the androgen receptor, and report replicated associations for five SNPs on chromosome 20p11.

Adult kidney organoids, or tubuloids, originate from CD24⁺ epithelial cells. Tubuloids represent a functional kidney tubule and can be used to model autosomal dominant polycystic kidney disease and study drug response.

Wang et al. profiled T cells in atherosclerotic plaques, artery tertiary lymphoid organs, and lymph nodes in mice with advanced atherosclerosis by single-cell RNA sequencing paired with T cell antigen receptor sequencing and observed complex patterns of deteriorating peripheral T cell tolerance. Signs of CD8⁺ tolerance dysfunction were found also in human plaques transcriptomic data, indicating that atherosclerosis can be considered as a bona fide T cell autoimmune disease.

The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.

A multi-ancestry genome-wide association study of problematic alcohol use in one million individuals identified 110 risk variants and shows that multi-ancestry polygenic scores improve risk prediction compared with single-ancestry scores

Ultrasound-mediated blood-brain barrier opening has been exploited to improve drug delivery in the brain. Here the authors show that low-intensity pulsed ultrasound in combination with intravenous injection of microbubbles enhances the delivery of doxorubicin and anti-PD1 in gliomas, improving anti-tumor immune responses.

Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation.

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.

ApoE is a direct checkpoint inhibitor of unresolvable inflammation in neurodegenerative and cardiovascular diseases

Andrew Singleton, Thomas Gasser and colleagues report results of a genome-wide association study of Parkinson's disease among individuals of European ancestry. They find genome-wide significant associations at two loci, SNCA and MAPT, and provide supporting evidence for a new risk locus on 1q32.

Stefan Schreiber and colleagues report the results of a genome-wide association study for ulcerative colitis. Variants flanking the gene encoding the cytokine IL10 are associated with increased risk of disease, as are several other loci.

Andre Franke and colleagues report results of a genome-wide association and replication study of ulcerative colitis. They identify two new regions of association at 7q22 and at 22q13 in IL17REL.

Stefan Schreiber and colleagues report the results of a genome-wide association study for sarcoidosis, a complex chronic inflammatory disorder. Variants near ANXA11 and PLAC9 are associated with elevated risk of the disease, with ANXA11 as the stronger candidate.

André Reis and colleagues report a genome-wide association study identifying a susceptibility locus at TRAF3IP2 for psoriatic arthritis and psoriasis.

Two methods fully resolve the GBA gene: Gauchian, a tool for short-read, whole-genome sequencing data analysis, and Oxford Nanopore sequencing after PCR enrichment. The approach improves our understanding of the relationship between GBA, Gaucher disease and Parkinson disease.

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.