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Fibromuscular dysplasia is a cardiovascular disease affecting mostly women with a mostly unknown genetic basis. Here the authors have performed a genome-wide association meta-analysis of Fibromuscular dysplasia to identify genetic loci, some of which are shared with common cardiovascular disease and traits.

Polygenic scores are believed to hold future promise for trait prediction and personalized medicine, but are sensitive to demographic history. Here, Marnetto et al. develop partial polygenic scores supplemented with local ancestry deconvolution which improves prediction accuracy into recently admixed European populations.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Open Targets Genetics is a community resource that provides systematic fine mapping at human GWAS loci, enabling users to prioritize genes at disease-associated regions and assess their potential as drug targets.

Here the authors used an evidence-based strategy to prioritize causal pleiotropic variants of autoimmune diseases, and revealed  that rs4728142 modulates aberrant IRF5 alternative promoter usage by ZBTB3-mediated chromatin looping.

MC3R deficiency is associated with a delay in the onset of puberty, and a reduction in growth and lean mass.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

Using genetic and demographic data from the UK Biobank, the authors clustered 116 common diseases based on their age-of-onset profiles and found increased genetic similarity within clusters, suggesting common etiologies. Two of the four disease clusters were associated with aging-related genes but differed in functional enrichment and evolutionary profiles.

Genome-wide analyses in BioBank Japan, UK Biobank and FinnGen identify ~5,000 new loci associated with 220 human traits. Statistical decomposition of matrices of phenome-wide summary statistics further highlights variants underpinning diseases across populations.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

The cross-population Sum of Single Effects (SuSiEx) model is a robust and computationally efficient method for conducting multi-ancestry fine-mapping of genome-wide association signals, producing smaller credible sets and capturing population-specific causal variants.

Integrated use of an animal model, a biobank for common diseases and a rare Mendelian disease leads to the discovery of a new syndrome and its pathological mechanism.

A GWAS of lifetime cannabis use reveals new risk loci, shows that cannabis use has genetic overlap with smoking and alcohol use, and indicates that the likelihood of initiating cannabis use is causally influenced by schizophrenia.

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.

Schmidt et al. use Mendelian randomization to identify (biventricular) cardiac MRI measurements with a strong association with heart failure and/or atrial fibrillation. Nine cardiac MRI measurements are identified that may be relevant to consider as surrogate outcomes in both research and clinical settings.

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.

Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. Here, the authors conduct a GWAS and suggest protective effect of higher TSH on risk of thyroid cancer and goitre.

Predominant participation of European-ancestry individuals in genetic studies has hindered the better understanding of genetic risk in non-European ancestry individuals. Here, Duncan et al. quantify polygenic risk score use and performance in worldwide populations.

 An analysis of rare coding variants across 22 common traits and diseases indicates that these variants will contribute substantially to biological insights but modestly to population risk stratification.

The generation of a national pan-genome, a population-specific catalogue of genetic variation, may advance the impact of clinical genetics studies. Here the Besenbacher et al. carry out deep sequencing and de novo assembly of 10 parent–child trios to generate a Danish pan-genome that provides insight into structural variation, de novomutation rates and variant calling.

Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. In this study, the authors use RNA sequencing analyses to characterize differences in the transcriptome between autistic and typically developing brains.

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.

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.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

The authors characterize immune response in Omicron-infected vaccinated individuals and observe an immune enhancement. While increases in neutralizing antibodies and spike T cells are stronger in previously naïve individuals, mucosal antibodies and non-spike responses increase regardless of infection history.

Aberrant changes in DNA methylation have been implicated in various neurodevelopmental disorders but remain under studied in developmental and epileptic encephalopathies. Here, the authors demonstrate the diagnostic utility of genome-wide DNA methylation analyses toward identifying molecular etiologies in developmental and epileptic encephalopathies.