Heritability of nonalcoholic fatty liver disease.
OBJECTIVE
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.
Schwimmer
Jeffrey B
JB
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California 92103, USA. jschwimmer@ucsd.edu
Celedon
Manuel A
MA
Lavine
Joel E
JE
Salem
Rany
R
Campbell
Nzali
N
Schork
Nicholas J
NJ
Shiehmorteza
Masoud
M
Yokoo
Takeshi
T
Chavez
Alyssa
A
Middleton
Michael S
MS
Sirlin
Claude B
CB
D000293:Adolescent; D000328:Adult; D002648:Child; D005234:Fatty Liver / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000150:complications; D050177:Overweight / Q000150:complications; D010290:Parents; D010375:Pedigree; D035781:Siblings