Faculty, Staff and Student Publications
Language
English
Publication Date
7-1-2024
Journal
Nutrition, Metabolism and Cardiovascular Diseases
DOI
10.1016/j.numecd.2024.03.002
PMID
38555241
PMCID
PMC12086968
PubMedCentral® Posted Date
5-29-2025
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 (h2± 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.
Keywords
Humans, Female, Male, Middle Aged, Adult, Adiposity, Aged, Longitudinal Studies, Adolescent, Young Adult, Phenotype, Aged, 80 and over, Genetic Predisposition to Disease, Liver, Heredity, United States, Non-alcoholic Fatty Liver Disease, Fatty Liver, Magnetic Resonance Imaging, Risk Assessment, Genetic Association Studies, Non-Alcoholic Fatty Liver Disease, Pleiotropy, Adiposity, Ectopic Fat, Metabolic Health, Steatotic Liver Disease, Metabolic Dysfunction Associated Steatotic Liver Disease
Published Open-Access
yes
Recommended Citation
Garza, Ariana L; Lee, Miryoung; Blangero, John; et al., "Genetic Correlations Between Liver Fat Content, Metabolic Health, and Adiposity Distribution in the Fels Longitudinal Study" (2024). Faculty, Staff and Student Publications. 1136.
https://digitalcommons.library.tmc.edu/uthsph_docs/1136