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Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

In rare diseases, rare mutations have long been thought of as the only contributor. Genetic analyses of people with such conditions now suggest that the effects of common genetic variants can stack up and contribute to disease risk.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Using genome-wide meta-analyses of clinical measures of depression and biobank data, the authors investigate symptom-specific genetic associations between depression and subsequent risk for Alzheimer’s disease, finding an absence of a putative genetic overlap between disorders.

A new GWAS of schizophrenia (11,260 cases and 24,542 controls) and meta-analysis identifies 50 new associated loci and 145 loci in total. The common variant association signal is highly enriched in mutation-intolerant genes and in regions under strong background selection.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Psychiatric disorders are often accompanied by alterations in BMI and body composition due to changes in eating behaviour and physical activity. Here, Hübel et al. study the genetic overlap between these traits and find that genetic correlations between psychiatric disorders and body composition are sex-specific and evident only in adulthood.

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.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Cognitive variability with age has been examined in 21,051 recallable volunteers and has highlighted a potential role of microglia and glycogen metabolism in the individual differences in general cognitive ability.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Pamela Sklar and colleagues report a genome-wide association study of bipolar disorder and identify variants in the genes encoding ankyrin-3 and the alpha-1C subunit of the L-type voltage-gated calcium channel as increasing risk.

Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

Whole-exome sequencing identifies ten risk genes for schizophrenia implicated by rare protein-coding variants, a subset of which overlap with risk genes in other neurodevelopmental disorders.

Integration of single-cell RNA sequencing with genome-wide association data implicates specific brain cell types in schizophrenia. Gene sets previously associated with schizophrenia implicate the same cell types, which include pyramidal cells and medium spiny neurons.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Understanding how parents’ cognitive and non-cognitive skills influence their children’s educational trajectories is important for educational, family and economic policy. Here, the authors investigate parental influence on children’s education using genetic approaches.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Here, the authors used electronic healthcare records to analyse the genetic basis of variation in 42 routinely-acquired quantitative blood tests among up to 40,000 British South Asian volunteers from the Genes and Health study. By combining their results with genetic findings from UK Biobank, they explore similarities and differences between ancestries in the genetic basis of these traits.

Joint analysis of 11 major psychiatric disorders identifies four broad factor underlying genetic correlations among the disorders. Association analyses detect 152 loci acting on these factors and identify 9 loci that act heterogeneously across disorders.

Ammar Al-Chalabi, Jan Veldink and colleagues perform a genome-wide association study for amyotrophic lateral sclerosis (ALS) in 15,156 cases and 26,242 controls. They identify three new genome-wide-significant variants and establish ALS as a complex trait with a polygenic architecture, but with a distinct and important role for low-frequency variants.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

In a cohort of 50,556 South Asian individuals, partitioned polygenic scores helped identify genetic susceptibility to insulin deficiency and unfavorable fat distribution as key drivers of young-onset T2D diagnosis and faster progression to diabetes-related complications.

The authors conducted a genetic meta-analysis of depression and found 269 associated genes. These genes highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The UK Biobank provides data for three depression-related phenotypes. Here, Howard et al. perform a genome-association study for broad depression, probable major depressive disorder (MDD) and hospital record-coded MDD in up to 322,580 UK Biobank participants which highlights excitatory synaptic pathways.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Meta-analysis of genome-wide association studies for cognitive ability identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure.