Genetic Variants Associated with Obesity and Insulin Resistance in Hispanic Boys with Nonalcoholic Fatty Liver Disease

John C. Rausch, Joel E. Lavine, Naga Chalasani, Xiuqing Guo, Soonil Kwon, Jeffrey B. Schwimmer, Jean P. Molleston, Rohit Loomba, Elizabeth M. Brunt, Yii Der Ida Chen, Mark O. Goodarzi, Kent D. Taylor, Katherine Yates, Jerome I. Rotter

Research output: Contribution to journalArticle

Abstract

Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. Methods: We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with P value <10 -5 and a minor allele frequency >5% were considered potentially significant. Results: Evaluated subjects had a median age of 12.0 years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH, and definite NASH were 23%, 53%, and 22%, respectively. The GWAS identified 10 SNPs that were associated with BMI z score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). Conclusions: This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.

Original languageEnglish (US)
Pages (from-to)789-796
Number of pages8
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume66
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Hispanic Americans
Insulin Resistance
Obesity
Genome-Wide Association Study
Single Nucleotide Polymorphism
Body Mass Index
Biopsy
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 2
Gluconeogenesis
Chromosomes, Human, Pair 1
Adiposity
Non-alcoholic Fatty Liver Disease
Linear Models
Hemoglobins
Cohort Studies
Prospective Studies
Liver
Research
Population

Keywords

  • insulin resistance
  • nonalcoholic fatty liver disease
  • obesity
  • steatohepatitis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

Cite this

Genetic Variants Associated with Obesity and Insulin Resistance in Hispanic Boys with Nonalcoholic Fatty Liver Disease. / Rausch, John C.; Lavine, Joel E.; Chalasani, Naga; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey B.; Molleston, Jean P.; Loomba, Rohit; Brunt, Elizabeth M.; Chen, Yii Der Ida; Goodarzi, Mark O.; Taylor, Kent D.; Yates, Katherine; Rotter, Jerome I.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 66, No. 5, 01.05.2018, p. 789-796.

Research output: Contribution to journalArticle

Rausch, JC, Lavine, JE, Chalasani, N, Guo, X, Kwon, S, Schwimmer, JB, Molleston, JP, Loomba, R, Brunt, EM, Chen, YDI, Goodarzi, MO, Taylor, KD, Yates, K & Rotter, JI 2018, 'Genetic Variants Associated with Obesity and Insulin Resistance in Hispanic Boys with Nonalcoholic Fatty Liver Disease', Journal of Pediatric Gastroenterology and Nutrition, vol. 66, no. 5, pp. 789-796. https://doi.org/10.1097/MPG.0000000000001926
Rausch, John C. ; Lavine, Joel E. ; Chalasani, Naga ; Guo, Xiuqing ; Kwon, Soonil ; Schwimmer, Jeffrey B. ; Molleston, Jean P. ; Loomba, Rohit ; Brunt, Elizabeth M. ; Chen, Yii Der Ida ; Goodarzi, Mark O. ; Taylor, Kent D. ; Yates, Katherine ; Rotter, Jerome I. / Genetic Variants Associated with Obesity and Insulin Resistance in Hispanic Boys with Nonalcoholic Fatty Liver Disease. In: Journal of Pediatric Gastroenterology and Nutrition. 2018 ; Vol. 66, No. 5. pp. 789-796.
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abstract = "Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. Methods: We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with P value <10 -5 and a minor allele frequency >5{\%} were considered potentially significant. Results: Evaluated subjects had a median age of 12.0 years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH, and definite NASH were 23{\%}, 53{\%}, and 22{\%}, respectively. The GWAS identified 10 SNPs that were associated with BMI z score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). Conclusions: This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.",
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T1 - Genetic Variants Associated with Obesity and Insulin Resistance in Hispanic Boys with Nonalcoholic Fatty Liver Disease

AU - Rausch, John C.

AU - Lavine, Joel E.

AU - Chalasani, Naga

AU - Guo, Xiuqing

AU - Kwon, Soonil

AU - Schwimmer, Jeffrey B.

AU - Molleston, Jean P.

AU - Loomba, Rohit

AU - Brunt, Elizabeth M.

AU - Chen, Yii Der Ida

AU - Goodarzi, Mark O.

AU - Taylor, Kent D.

AU - Yates, Katherine

AU - Rotter, Jerome I.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. Methods: We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with P value <10 -5 and a minor allele frequency >5% were considered potentially significant. Results: Evaluated subjects had a median age of 12.0 years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH, and definite NASH were 23%, 53%, and 22%, respectively. The GWAS identified 10 SNPs that were associated with BMI z score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). Conclusions: This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.

AB - Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. Methods: We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with P value <10 -5 and a minor allele frequency >5% were considered potentially significant. Results: Evaluated subjects had a median age of 12.0 years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH, and definite NASH were 23%, 53%, and 22%, respectively. The GWAS identified 10 SNPs that were associated with BMI z score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). Conclusions: This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.

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KW - nonalcoholic fatty liver disease

KW - obesity

KW - steatohepatitis

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