TY - JOUR
T1 - Heritability of Nonalcoholic Fatty Liver Disease
AU - Schwimmer, Jeffrey B.
AU - Celedon, Manuel A.
AU - Lavine, Joel E.
AU - Salem, Rany
AU - Campbell, Nzali
AU - Schork, Nicholas J.
AU - Shiehmorteza, Masoud
AU - Yokoo, Takeshi
AU - Chavez, Alyssa
AU - Middleton, Michael S.
AU - Sirlin, Claude B.
N1 - Funding Information:
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.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
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U2 - 10.1053/j.gastro.2009.01.050
DO - 10.1053/j.gastro.2009.01.050
M3 - Article
C2 - 19208353
AN - SCOPUS:65249188812
SN - 0016-5085
VL - 136
SP - 1585
EP - 1592
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -