Search

Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses. Here, Brumpton et al. describe theory and simulations for overcoming such biases in Mendelian randomization through within-family studies.

Myasthenia gravis (MG) is a rare autoantibody-mediated disease affecting the neuromuscular junction. Here, the authors discover common genetic variation associated with the disease, increasing understanding of the genetic basis.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

REM-sleep behavior disorder often precedes Parkinson’s disease or dementia. Here, the authors perform a genome-wide association study for REM-sleep behavior disorder, and discover how it potentially affects gene expression in the brain.

Using a battery of statistical tools, Alagöz et al. examine the genetic overlap between dyslexia and rhythm impairment and shed light on how the genome influences the neural bases of human language and musicality.

A genome-wide association study performed in 1,126,563 individuals identifies seven new loci associated with Alzheimer’s disease and implicates microglia and immune cells in late-onset disease.

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.

Matrix metalloproteinases (MMPs) normally act extracellularly. Now Marchant et al. report an unexpected nuclear activity for MMP-12 in virus-infected cells in regulating transcription of the gene encoding IκBα and affecting secretion of interferon-α.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers and have genetic overlap. Here, the authors use a multi-trait genetic and phenotypic analysis to reveal susceptibility loci for BCC and SCC, and report an optimised polygenic risk score for risk stratification.

Although varicose veins are a common condition, the genetic basis is not well understood. Here, the authors find genetic variants associated with varicose veins and show that a higher polygenic risk score for varicose veins correlates with a greater likelihood of patients undergoing surgical treatment.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Genetic analyses identify widespread sex-differential participation bias in population-based studies and show how this bias can lead to incorrect inferences. These findings highlight new challenges for association studies as sample sizes continue to grow.

Heart failure has a heterogeneous etiology and the genetic underpinnings are not well understood. Here, Arvanitis et al. perform GWAS meta-analysis including 10,976 heart failure cases and 437,573 controls, identify new loci near ABO and ACTN2 and show that deletion of a ACTN2 enhancer leads to reduced ACTN2 expression in differentiating cardiomyocytes.

Genome-wide analysis of self-reported dyslexia identifies 42 associated loci, including 27 not previously associated with cognitive traits. Dyslexia shows genetic correlation with ambidexterity but not neuroanatomical measures of language-related circuitry.

Genome-wide association meta-analysis of insomnia in 593,724 cases and 1,771,286 controls identifies 554 risk loci and implicates specific biological pathways through gene prioritization.

Niarchou et al. identify 69 genomic loci associated with people’s synchronization to a musical beat. The genetic architecture of beat synchronization was enriched for genes involved in early brain development and lifelong brain function.

Genome-wide association analysis of irritable bowel syndrome identifies genetic susceptibility loci and highlights shared pathways with mood and anxiety disorders.

The genetic basis of daytime napping and the directional effect of daytime napping on cardiometabolic health are unknown. Here, the authors perform a genome-wide association study on self-reported daytime napping in the UK Biobank and Mendelian randomization to explore causal associations.

Mendelian randomization analysis leveraging data from the UK Biobank and 23andMe, Inc., suggests that an individual’s sleep habits may impact those of their partner.

CT-SLEB, a powerful and scalable method, improves the performance of multiancestry polygenic prediction by generating polygenic risk scores based on GWAS summary statistics in diverse populations.

Stagaman et al. investigate the associations between early idiopathic Parkinson’s disease (PD) and the diversity and composition of both saliva and stool microbiomes in a large, geographically diverse US cohort. Abundances of saliva microbes, particularly Prevotella, Neisseria, and Streptococcus OTUs, best distinguish between controls and cases.

Puan and San Luis et al. find that FUT6, encoding a fucosyltransferase, is required for the “rolling” behavior of certain white blood cells that enables them to move from blood vessels to tissues. They show that FUT6 deficiency leads to a loss of the tetrasaccharide sLex on the surface of basophils, resulting in cells that are less sticky and therefore less able to form the necessary adhesions for exiting the blood vessel to drive the allergic reaction.

A large multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma, providing insight into the genetic basis of these serious forms of cancer.

O’Connell et al. construct a new genome-wide imputation reference panel comprising 2,269 individuals of Sub-Saharan African ancestries. They adapt DeepVariant to create best practices for reference panel development and generate a high quality, publicly available resource that will further empower high resolution genome-wide imputation efforts in individuals of African ancestries.