An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents

Research output: Contribution to journal › Journal article › Research › peer-review

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An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents. / Huang, Yun; Stinson, Sara E; Juel, Helene Baek; Lund, Morten A V; Holm, Louise Aas; Fonvig, Cilius E; Nielsen, Trine; Grarup, Niels; Pedersen, Oluf; Christiansen, Michael; Chabanova, Elizaveta; Thomsen, Henrik S; Krag, Aleksander; Stender, Stefan; Holm, Jens-Christian; Hansen, Torben.

In: Liver International, Vol. 43, No. 8, 2023, p. 1772-1782.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Huang, Y, Stinson, SE, Juel, HB, Lund, MAV, Holm, LA, Fonvig, CE, Nielsen, T, Grarup, N, Pedersen, O, Christiansen, M, Chabanova, E, Thomsen, HS, Krag, A, Stender, S, Holm, J-C & Hansen, T 2023, 'An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents', Liver International, vol. 43, no. 8, pp. 1772-1782. https://doi.org/10.1111/liv.15613

APA

Huang, Y., Stinson, S. E., Juel, H. B., Lund, M. A. V., Holm, L. A., Fonvig, C. E., Nielsen, T., Grarup, N., Pedersen, O., Christiansen, M., Chabanova, E., Thomsen, H. S., Krag, A., Stender, S., Holm, J-C., & Hansen, T. (2023). An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents. Liver International, 43(8), 1772-1782. https://doi.org/10.1111/liv.15613

Vancouver

Huang Y, Stinson SE, Juel HB, Lund MAV, Holm LA, Fonvig CE et al. An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents. Liver International. 2023;43(8):1772-1782. https://doi.org/10.1111/liv.15613

Author

Huang, Yun ; Stinson, Sara E ; Juel, Helene Baek ; Lund, Morten A V ; Holm, Louise Aas ; Fonvig, Cilius E ; Nielsen, Trine ; Grarup, Niels ; Pedersen, Oluf ; Christiansen, Michael ; Chabanova, Elizaveta ; Thomsen, Henrik S ; Krag, Aleksander ; Stender, Stefan ; Holm, Jens-Christian ; Hansen, Torben. / An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents. In: Liver International. 2023 ; Vol. 43, No. 8. pp. 1772-1782.

Bibtex

@article{45970278b2f447b9ab6498250013644d,
title = "An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents",
abstract = "BACKGROUND & AIMS: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents.APPROACH & RESULTS: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population-based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1 H-MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p < .05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1-SD unit: 2.17, p = 9.7E-10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76-0.81). Combining the GRS with clinical measures (waist-to-height ratio [WHtR] SDS, ALT, and HOMA-IR) increased the AUC up to 0.86 (95% CI 0.84-0.88). CONCLUSIONS: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification.",
author = "Yun Huang and Stinson, {Sara E} and Juel, {Helene Baek} and Lund, {Morten A V} and Holm, {Louise Aas} and Fonvig, {Cilius E} and Trine Nielsen and Niels Grarup and Oluf Pedersen and Michael Christiansen and Elizaveta Chabanova and Thomsen, {Henrik S} and Aleksander Krag and Stefan Stender and Jens-Christian Holm and Torben Hansen",
note = "{\textcopyright} 2023 The Authors. Liver International published by John Wiley & Sons Ltd.",
year = "2023",
doi = "10.1111/liv.15613",
language = "English",
volume = "43",
pages = "1772--1782",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "8",

}

RIS

TY - JOUR

T1 - An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents

AU - Huang, Yun

AU - Stinson, Sara E

AU - Juel, Helene Baek

AU - Lund, Morten A V

AU - Holm, Louise Aas

AU - Fonvig, Cilius E

AU - Nielsen, Trine

AU - Grarup, Niels

AU - Pedersen, Oluf

AU - Christiansen, Michael

AU - Chabanova, Elizaveta

AU - Thomsen, Henrik S

AU - Krag, Aleksander

AU - Stender, Stefan

AU - Holm, Jens-Christian

AU - Hansen, Torben

N1 - © 2023 The Authors. Liver International published by John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - BACKGROUND & AIMS: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents.APPROACH & RESULTS: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population-based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1 H-MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p < .05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1-SD unit: 2.17, p = 9.7E-10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76-0.81). Combining the GRS with clinical measures (waist-to-height ratio [WHtR] SDS, ALT, and HOMA-IR) increased the AUC up to 0.86 (95% CI 0.84-0.88). CONCLUSIONS: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification.

AB - BACKGROUND & AIMS: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents.APPROACH & RESULTS: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population-based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1 H-MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p < .05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1-SD unit: 2.17, p = 9.7E-10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76-0.81). Combining the GRS with clinical measures (waist-to-height ratio [WHtR] SDS, ALT, and HOMA-IR) increased the AUC up to 0.86 (95% CI 0.84-0.88). CONCLUSIONS: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification.

U2 - 10.1111/liv.15613

DO - 10.1111/liv.15613

M3 - Journal article

C2 - 37208954

VL - 43

SP - 1772

EP - 1782

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 8

ER -

ID: 347805062