A Case-Control Study Supports Genetic Contribution of the Gene Family in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease.

The paraoxonase () gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare variants on both conditions was investigated. A total of 507 healthy weight individuals and 744 patients with obesity including 433 with histological liver assessment, were sequenced with single-molecule molecular inversion probes (smMIPs), allowing the identification of genetic contributions to obesity and MASLD-related liver features.

Rare Heterozygous Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.

Recently, it was reported that heterozygous PCSK1 variants, causing partial PC1/3 deficiency, result in a significant increased risk for obesity. This effect was almost exclusively generated by the rare p.Y181H (rs145592525, GRCh38.

A targeted multi-omics approach reveals paraoxonase-1 as a determinant of obesity-associated fatty liver disease.

Background: The multifactorial nature of non-alcoholic fatty liver disease cannot be explained solely by genetic factors. Recent evidence revealed that DNA methylation changes take place at proximal promoters within susceptibility genes. This emphasizes the need for integrating multiple data types to provide a better understanding of the disease's pathogenesis.

Copy number variant analysis and expression profiling of the olfactory receptor-rich 11q11 region in obesity predisposition.

Genome-wide copy number surveys associated chromosome 11q11 with obesity. As this is an olfactory receptor-rich region, we hypothesize that genetic variation in olfactory receptor genes might be implicated in the pathogenesis of obesity. Multiplex Amplicon Quantification analysis was applied to screen for copy number variants at chromosome 11q11 in 627 patients with obesity and 330 healthy-weight individuals.

Insights into the multifactorial causation of obesity by integrated genetic and epigenetic analysis.

Obesity is a highly heritable multifactorial disease that places an enormous burden on human health. Its increasing prevalence and the concomitant-reduced life expectancy has intensified the search for new analytical methods that can reduce the knowledge gap between genetic susceptibility and functional consequences of the disease pathology. Although the influence of genetics and epigenetics has been studied independently in the past, there is increasing evidence that genetic variants interact with environmental factors through epigenetic regulation.