Heritability of Nonalcoholic Fatty Liver Disease

Jeffrey B. Schwimmer, 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1585-1592
Number of pages8
JournalGastroenterology
Volume136
Issue number5
DOIs
StatePublished - May 2009

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Fatty Liver
Fats
Liver
Non-alcoholic Fatty Liver Disease
Siblings
Body Mass Index
Parents
Liver Diseases
Analysis of Variance
Chronic Disease
Magnetic Resonance Imaging
Biopsy
Genes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Schwimmer, J. B., Celedon, M. A., Lavine, J. E., Salem, R., Campbell, N., Schork, N. J., ... Sirlin, C. B. (2009). Heritability of Nonalcoholic Fatty Liver Disease. Gastroenterology, 136(5), 1585-1592. https://doi.org/10.1053/j.gastro.2009.01.050

Heritability of Nonalcoholic Fatty Liver Disease. / Schwimmer, Jeffrey B.; Celedon, Manuel A.; Lavine, Joel E.; Salem, Rany; Campbell, Nzali; Schork, Nicholas J.; Shiehmorteza, Masoud; Yokoo, Takeshi; Chavez, Alyssa; Middleton, Michael S.; Sirlin, Claude B.

In: Gastroenterology, Vol. 136, No. 5, 05.2009, p. 1585-1592.

Research output: Contribution to journalArticle

Schwimmer, JB, Celedon, MA, Lavine, JE, Salem, R, Campbell, N, Schork, NJ, Shiehmorteza, M, Yokoo, T, Chavez, A, Middleton, MS & Sirlin, CB 2009, 'Heritability of Nonalcoholic Fatty Liver Disease', Gastroenterology, vol. 136, no. 5, pp. 1585-1592. https://doi.org/10.1053/j.gastro.2009.01.050
Schwimmer JB, Celedon MA, Lavine JE, Salem R, Campbell N, Schork NJ et al. Heritability of Nonalcoholic Fatty Liver Disease. Gastroenterology. 2009 May;136(5):1585-1592. https://doi.org/10.1053/j.gastro.2009.01.050
Schwimmer, Jeffrey B. ; Celedon, Manuel A. ; Lavine, Joel E. ; Salem, Rany ; Campbell, Nzali ; Schork, Nicholas J. ; Shiehmorteza, Masoud ; Yokoo, Takeshi ; Chavez, Alyssa ; Middleton, Michael S. ; Sirlin, Claude B. / Heritability of Nonalcoholic Fatty Liver Disease. In: Gastroenterology. 2009 ; Vol. 136, No. 5. pp. 1585-1592.
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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.",
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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.

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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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