Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.

Background: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability.

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Polygenic prediction of body mass index and obesity through the life course and across ancestries.

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.

Ensuring the structural integrity of tokamak fusion power plants: challenges, progress and pathway.

Structural integrity for fusion is an integrated multi-disciplinary subject spanning the science of materials, technology, engineering, health monitoring and simulation methods and algorithms for scrutinizing the assurance of reliable fusion reactor performance from the whole plant design phase through operation to decommissioning. Structural integrity is essential for maintaining high standards of public, environmental and investment protection and maximizing economic benefits. While fusion shares many of the structural integrity challenges faced by other industries, it also presents unique complexities.

Genome-wide association study and multi-ancestry meta-analysis identify common variants associated with carotid artery intima-media thickness.

Carotid artery intima-media thickness (cIMT) is a measurement of subclinical atherosclerosis that predicts future cardiovascular events, including stroke and myocardial infarction. Genome-wide association studies (GWAS) have identified only a fraction of the genetic variants associated with cIMT. We performed the largest GWAS for cIMT involving up to 131,000 individuals.