Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. Study design: There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. Results: The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7-07). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9-07). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. Conclusions: In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies.

Original languageEnglish (US)
JournalJournal of Pediatrics
DOIs
StateAccepted/In press - 2017

Fingerprint

Hispanic Americans
Histology
Genome
Liver
Single Nucleotide Polymorphism
Fibrosis
Genome-Wide Association Study
Regression Analysis
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 8
Genetic Loci
Non-alcoholic Fatty Liver Disease
Actins
Linear Models
Body Mass Index
Logistic Models
DNA
Research
Genes
Proteins

Keywords

  • Fatty liver
  • Fibrosis
  • Genome wide
  • Hispanic
  • Pediatrics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys. / Wattacheril, Julia; Lavine, Joel E.; Chalasani, Naga; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean; Loomba, Rohit; Brunt, Elizabeth M.; Chen, Yii Der Ida; Goodarzi, Mark O.; Taylor, Kent D.; Yates, Katherine P.; Tonascia, James; Rotter, Jerome I.

In: Journal of Pediatrics, 2017.

Research output: Contribution to journalArticle

Wattacheril, J, Lavine, JE, Chalasani, N, Guo, X, Kwon, S, Schwimmer, J, Molleston, J, Loomba, R, Brunt, EM, Chen, YDI, Goodarzi, MO, Taylor, KD, Yates, KP, Tonascia, J & Rotter, JI 2017, 'Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys', Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2017.08.004
Wattacheril, Julia ; Lavine, Joel E. ; Chalasani, Naga ; Guo, Xiuqing ; Kwon, Soonil ; Schwimmer, Jeffrey ; Molleston, Jean ; Loomba, Rohit ; Brunt, Elizabeth M. ; Chen, Yii Der Ida ; Goodarzi, Mark O. ; Taylor, Kent D. ; Yates, Katherine P. ; Tonascia, James ; Rotter, Jerome I. / Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys. In: Journal of Pediatrics. 2017.
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abstract = "Objective: To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. Study design: There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. Results: The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7-07). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9-07). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. Conclusions: In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies.",
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T1 - Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys

AU - Wattacheril, Julia

AU - Lavine, Joel E.

AU - Chalasani, Naga

AU - Guo, Xiuqing

AU - Kwon, Soonil

AU - Schwimmer, Jeffrey

AU - Molleston, Jean

AU - Loomba, Rohit

AU - Brunt, Elizabeth M.

AU - Chen, Yii Der Ida

AU - Goodarzi, Mark O.

AU - Taylor, Kent D.

AU - Yates, Katherine P.

AU - Tonascia, James

AU - Rotter, Jerome I.

PY - 2017

Y1 - 2017

N2 - Objective: To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. Study design: There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. Results: The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7-07). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9-07). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. Conclusions: In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies.

AB - Objective: To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. Study design: There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. Results: The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7-07). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9-07). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. Conclusions: In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies.

KW - Fatty liver

KW - Fibrosis

KW - Genome wide

KW - Hispanic

KW - Pediatrics

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