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Background & AimsNonalcoholic 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. MethodsOverweight 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. ResultsFatty 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. ConclusionsFamily 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. Abbreviations used in this paper: BMI, body mass index, h2, narrow sense heritability, MRI, magnetic resonance imaging, NAFLD, nonalcoholic fatty liver disease, NASH, nonalcoholic steatohepatitis ⁎ Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California ∥ Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California ‡ Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California § Scripps Genomic Medicine and The Scripps Translational Sciences Institute, Scripps Health and The Scripps Research Institute, La Jolla, California
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. PII: S0016-5085(09)00152-8 doi:10.1053/j.gastro.2009.01.050 © 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
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ABSTRACT
Heritability of Nonalcoholic Fatty Liver Disease