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.
Subject(s)
Adiposity , Genetic Predisposition to Disease , Phenotype , Humans , Female , Male , Middle Aged , Adult , Adiposity/genetics , Aged , Longitudinal Studies , Adolescent , Young Adult , Aged, 80 and over , Liver/pathology , Liver/metabolism , Heredity , United States/epidemiology , Non-alcoholic Fatty Liver Disease/genetics , Fatty Liver/genetics , Magnetic Resonance Imaging , Risk Assessment , Genetic Association StudiesABSTRACT
BACKGROUND: Disease patterns in Mexican American health-disparity populations differ from larger US populations. AIMS: This study is aimed to determine frequency of gastrointestinal cancers in Mexican Americans. METHODS: We analyzed self-reported data from the Cameron County Hispanic Cohort where we find high rates of risk factors for cancer: obesity (48.5 %) and diabetes (30.7 %). Participants provided cancer histories about themselves and first- and second-degree relatives. Logistic regression models assessed risk factors. Frequencies of cancer sites were ranked and validated using concurrent age local cancer registry data. RESULTS: Among 9,249 individuals (participants and their relatives), there were 1,184 individuals with reports of cancer. Among cohort participants under 70 years of age, the most significant risk factor for all-cause cancers was diabetes (OR 3.57, 95 % CI 1.32, 9.62). Participants with metabolic syndrome were significantly more likely to report cancer in relatives [1.73 (95 % CI 1.26, 2.37]. Among cancers in fathers, liver cancer was ranked third, stomach fourth, colorectal sixth, and pancreas tenth. In mothers, stomach was third, liver fourth, colorectal seventh, and pancreas eleventh. The unusual prominence of these cancers in Mexican Americans, including liver cancer, was supported by age-adjusted incidence in local registry data. CONCLUSIONS: Gastrointestinal system cancers, particularly, liver cancer, in a Mexican American health disparity cohort and their relatives rank higher than in other ethnicities and are associated with high rates of diabetes and metabolic syndrome. Effective prevention of diabetes and low-tech, high-quality screening strategies for gastrointestinal cancers are needed in health disparity communities.
