Genetic correlations between liver fat content, metabolic health, and adiposity distribution in the Fels Longitudinal Study
Year: 2024
Type: article
Study design: Observational Study
Abstract: Background and Aims Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults. Methods and results 704 participants (18-95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait pairs. Mean liver fat was 5.95% (SE = 0.23) and steatosis (liver fat >5.56%) was present in 29.8% of participants. Heritability (h 2 ± SE) of steatosis was 0.72 ± 0.17 (p = 6.80e -6 ). All other traits including liver enzymes, fasting glucose, HOMA-IR, visceral and subcutaneous adipose tissue (VAT, SAT), body mass index, body fat percent, waist circumference, lipids and blood pressure were also heritable. Significant genetic correlations were found between liver fat and all traits except aspartate aminotransferase (AST), and among most trait pairs. Highest genetic correlations were between liver fat and HOMA-IR (0.85 ± 0.08, p=1.73e -8 ), fasting glucose and ALT (0.89 ± 0.26, p=6.68e -5 ), and HOMA-IR with: waist circumference (0.81 ± 0.12, p=3.76e -6 ), body fat percent (0.78 ± 0.12 p=2.42e -5 ) and VAT (0.73 ± 0.07, p=6.37e -8 ). Conclusions Common genes may exist between liver fat accumulation, metabolic features and adiposity phenotypes.
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: Cancer Prevention and Research Institute of Texas, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Collaborative Training of a New Cadre of Innovative Cancer Prevention Researchers, Adiposity, Disease Risk Factors, and Lifetime Health, Identification of the Exposome in Fatty Liver Disease in Mexican American Families Using Genetic Correction, G7984644244, Telomere Length Dynamics in Relation to Changes in Adiposity and Metabolic Risk, UTRGV Center for Genome Research, Cancer Prevention and Control Research Training and Career Development Program
OpenAlex ID: W4392519649