Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 May;136(5):1585-92.
doi: 10.1053/j.gastro.2009.01.050. Epub 2009 Jan 25.

Heritability of nonalcoholic fatty liver disease

Jeffrey B Schwimmer  1 , Manuel A Celedon, Joel E Lavine, Rany Salem, Nzali Campbell, Nicholas J Schork, Masoud Shiehmorteza, Takeshi Yokoo, Alyssa Chavez, Michael S Middleton, Claude B Sirlin
Affiliations

Heritability of nonalcoholic fatty liver disease

Jeffrey B Schwimmer et al. Gastroenterology. 2009 May.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interests: no conflicts of interest exist

Figures

Figure 1
Figure 1. Correlation of BMI and Liver Fat Fraction
Panel A: the correlation between BMI and liver fat fraction was high (r2 = 0.61; p < 0.01) in family members of children with NAFLD (●). Panel B: the correlation (r2 = 0.26; p < 0.05) between BMI and liver fat fraction was low in family members of children without NAFLD ( ). The difference in correlation was significant (p =0.029).
Figure 2
Figure 2. Paradigmatic pedigree of a child with NAFLD
The arrow indicates the proband, a girl with biopsy-proven NAFLD. She is shown to be obese (left upper box with grey fill), have an elevated ALT (right upper box with black fill) and to have a liver fat fraction > 5% (bottom box with striped fill). Her family can be seen to have only 1 other obese individual, 3 other with an elevated ALT, but fatty liver in all sibliings and parents.
See this image and copyright information in PMC

Comment in

References

    1. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of Fatty Liver in Children and Adolescents. Pediatrics. 2006;118:1388–1393. - PubMed
    1. Beymer C, Kowdley KV, Larson A, Edmonson P, Dellinger EP, Flum DR. Prevalence and Predictors of Asymptomatic Liver Disease in Patients Undergoing Gastric Bypass Surgery. Arch Surg. 2003;138:1240–1244. - PubMed
    1. Xanthakos S, Miles L, Bucuvalas J, Daniels S, Garcia V, Inge T. Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents. Clinical Gastro Hep. 2006;4:226–2332. - PubMed
    1. Kim HJ, Lee KE, Kim DJ, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med. 2004;164:2169–2175. - PubMed
    1. Nobili V, Marcellini M, Devito R, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology. 2006;44:458–465. - PubMed

Publication types