Gastroenterology

Gastroenterology

Volume 136, Issue 5, May 2009, Pages 1585-1592
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
Heritability of Nonalcoholic Fatty Liver Disease

https://doi.org/10.1053/j.gastro.2009.01.050Get rights and content

Background & Aims

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The etiology is believed to be multifactorial with a substantial genetic component; however, the heritability of NAFLD is undetermined. Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable.

Methods

Overweight children with biopsy-proven NAFLD and overweight children without NAFLD served as probands. Family members were studied, including the use of magnetic resonance imaging to quantify liver fat fraction. Fatty liver was defined as a liver fat fraction of 5% or higher. Etiologies for fatty liver other than NAFLD were excluded. Narrow-sense heritability estimates for fatty liver (dichotomous) and fat fraction (continuous) were calculated using variance components analysis adjusted for covariate effects.

Results

Fatty liver was present in 17% of siblings and 37% of parents of overweight children without NAFLD. Fatty liver was significantly more common in siblings (59%) and parents (78%) of children with NAFLD. Liver fat fraction was correlated with body mass index, although the correlation was significantly stronger for families of children with NAFLD than those without NAFLD. Adjusted for age, sex, race, and body mass index, the heritability of fatty liver was 1.000 and of liver fat fraction was 0.386.

Conclusions

Family members of children with NAFLD should be considered at high risk for NAFLD. These data suggest that familial factors are a major determinant of whether an individual has NAFLD. Studies examining the complex relations between genes and environment in the development and progression of NAFLD are warranted.

Section snippets

Probands

Because most children with NAFLD are overweight or obese, all probands were required to be overweight or obese.15 Probands were further selected on the basis of the presence or absence of NAFLD. The diagnosis of NAFLD was based on the following: (1) liver biopsy with at least 5% or greater of hepatocytes containing macrovesicular fat,16 and (2) exclusion of other causes of chronic liver disease including hepatitis B (hepatitis B surface antigen), hepatitis C (hepatitis C antibody), α-1

Description of Probands

Details for the probands are shown in Table 1. There were 33 children with biopsy-proven NAFLD and 11 children without NAFLD. Age and BMI did not differ between the groups. The distribution of overweight and obesity also was the same for both groups: 18% overweight and 82% obese. The racial and ethnic distribution for children with NAFLD was as follows: 23 of 33 (70%) were white Hispanic, 7 of 33 (21%) were white non-Hispanic, and 3 of 33 (9%) were Native American Indian Hispanic. For children

Discussion

We performed a familial aggregation study of fatty liver in overweight children with and without NAFLD. In family members, the presence or absence of fatty liver was documented using MRI. Clinical history and laboratory testing were applied to exclude participants with alternate explanations for fatty liver other than NAFLD. The main finding was that liver fat fraction and the condition of fatty liver are heritable traits. The estimate for the heritability of the fatty liver as a dichotomous

Acknowledgments

The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

References (39)

  • C. Namikawa et al.

    Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis

    J Hepatol

    (2004)
  • J.B. Schwimmer et al.

    Prevalence of fatty liver in children and adolescents

    Pediatrics

    (2006)
  • C. Beymer et al.

    Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery

    Arch Surg

    (2003)
  • H.J. Kim et al.

    Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults

    Arch Intern Med

    (2004)
  • V. Nobili et al.

    NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice

    Hepatology

    (2006)
  • J.D. Browning et al.

    Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity

    Hepatology

    (2004)
  • J.D. Browning et al.

    Ethnic differences in the prevalence of cryptogenic cirrhosis

    Am J Gastroenterol

    (2004)
  • L.S. Szczepaniak et al.

    Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population

    Am J Physiol Endocrinol Metab

    (2005)
  • J.B. Schwimmer et al.

    The influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents

    Pediatrics

    (2005)
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    Conflict of interest The authors disclose no conflicts.

    Funding This work was funded in part by grants from the National Institutes of Health including R21 DK71486 from the National Institute of Diabetes and Digestive and Kidney Diseases, P60 MD00220 for the San Diego EXPORT Center from the National Center of Minority Health and Health Disparities, and M01 RR000827 from the National Center for Research Resources for the General Clinical Research Center at University of California, San Diego, and grant DK080506 from the UCSD Digestive Diseases Research Development Center, San Diego. Dr Salem and Dr Schork are supported in part by Scripps Genomic Medicine and The Scripps Translational Sciences Institute.

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