HETEROGENEITY ANALYSIS OF ASSOCIATIONS INVOLVING THE LARGE SCALE ONLINE MINDCROWD SURVEY MEMORY TEST.

Alzheimer's disease and related disorders (ADRD), as well as general age-related cognitive decline, are known to be multifactorial with heterogeneous etiologies. Identifying and accommodating heterogeneity in any one data set can be pursued using different analytical techniques, each with different assumptions or purposes. Whereas a great deal of research has explored clustering individuals of variables that exhibit greater similarity in some way, little research has explored evidence for heterogeneity in the relationships between relevant outcomes, such as a performance on a memory test, and risk factors such as environmental exposures, behaviors or genetic factors among individuals.

Genetic variants influencing liver fat in normal-weight individuals of European ancestry.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs across a wide spectrum of body weights, yet the genetic determinants underlying hepatic steatosis in individuals with normal BMI remain underexplored. This study aimed to identify genetic variants associated with liver fat fraction in normal-weight individuals.

Methods: We performed a genome-wide association study (GWAS) using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) data from 10,918 normal-weight participants (BMI <25 kg/m) of European ancestry in the UK Biobank.

The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank.

Large-scale genome-wide association studies (GWAS) strongly suggest that most traits and diseases have a polygenic component. This observation has motivated the development of disease-specific "polygenic scores (PGS)" that are weighted sums of the effects of disease-associated variants identified from GWAS that correlate with an individual's likelihood of expressing a specific phenotype. Although most GWAS have been pursued on disease traits, leading to the creation of refined "Polygenic Risk Scores" (PRS) that quantify risk to diseases, many GWAS have also been pursued on extreme human longevity, general fitness, health span, and other health-positive traits.

Hepatic PEMT Expression Decreases with Increasing NAFLD Severity.

Choline deficiency causes hepatic fat accumulation, and is associated with a higher risk of nonalcoholic fatty liver disease (NAFLD) and more advanced NAFLD-related hepatic fibrosis. Reduced expression of hepatic phosphatidylethanolamine N-methyltransferase (PEMT), which catalyzes the production of phosphatidylcholine, causes steatosis, inflammation, and fibrosis in mice. In humans, common PEMT variants impair phosphatidylcholine synthesis, and are associated with NAFLD risk.