Genetic variation and elevated liver enzymes during childhood, adolescence and early adulthood
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Genetic variation and elevated liver enzymes during childhood, adolescence and early adulthood. / Stender, Stefan; Davey Smith, George; Richardson, Tom G.
In: International Journal of Epidemiology, Vol. 52, No. 5, 2023, p. 1341-1349.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic variation and elevated liver enzymes during childhood, adolescence and early adulthood
AU - Stender, Stefan
AU - Davey Smith, George
AU - Richardson, Tom G
N1 - © The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: Genetic factors influence the risk of fatty liver disease (FLD) in adults. The aim of this study was to test if, and when, genetic risk factors known to affect FLD in adults begin to exert their deleterious effects during childhood, adolescence and early adulthood.METHODS: We included up to 4018 British children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Three genetic variants known to associate robustly with FLD in adults (PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567) were tested for association with plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) during childhood (mean age: 9.9 years), early adolescence (15.5 years), late adolescence (17.8 years), and early adulthood (24.5 years). We also tested the associations of a 17-variant score and whole-genome polygenic risk scores (PRS) derived from associations in adults with plasma ALT and AST at the same four time points. Associations with elastography-derived liver steatosis and fibrosis were tested in early adulthood.RESULTS: Genetic risk factors for FLD (individually, combined into a 3-variant score, a 17-variant score and as a genome-wide PRS), were associated with higher liver enzymes, beginning in childhood and throughout adolescence and early adulthood. The ALT-increasing effects of the genetic risk variants became larger with increasing age. The ALT-PRS was associated with liver steatosis in early adulthood. No genetic associations with fibrosis were observed.CONCLUSIONS: Genetic factors that promote FLD in adults associate with elevated liver enzymes already during childhood, and their effects get amplified with increasing age.
AB - BACKGROUND: Genetic factors influence the risk of fatty liver disease (FLD) in adults. The aim of this study was to test if, and when, genetic risk factors known to affect FLD in adults begin to exert their deleterious effects during childhood, adolescence and early adulthood.METHODS: We included up to 4018 British children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Three genetic variants known to associate robustly with FLD in adults (PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567) were tested for association with plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) during childhood (mean age: 9.9 years), early adolescence (15.5 years), late adolescence (17.8 years), and early adulthood (24.5 years). We also tested the associations of a 17-variant score and whole-genome polygenic risk scores (PRS) derived from associations in adults with plasma ALT and AST at the same four time points. Associations with elastography-derived liver steatosis and fibrosis were tested in early adulthood.RESULTS: Genetic risk factors for FLD (individually, combined into a 3-variant score, a 17-variant score and as a genome-wide PRS), were associated with higher liver enzymes, beginning in childhood and throughout adolescence and early adulthood. The ALT-increasing effects of the genetic risk variants became larger with increasing age. The ALT-PRS was associated with liver steatosis in early adulthood. No genetic associations with fibrosis were observed.CONCLUSIONS: Genetic factors that promote FLD in adults associate with elevated liver enzymes already during childhood, and their effects get amplified with increasing age.
KW - Adolescent
KW - Adult
KW - Child
KW - Humans
KW - Alanine Transaminase/blood
KW - Aspartate Aminotransferases/blood
KW - Fibrosis
KW - Genetic Predisposition to Disease
KW - Longitudinal Studies
KW - Non-alcoholic Fatty Liver Disease/genetics
KW - Polymorphism, Single Nucleotide
U2 - 10.1093/ije/dyad048
DO - 10.1093/ije/dyad048
M3 - Journal article
C2 - 37105232
VL - 52
SP - 1341
EP - 1349
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
SN - 0300-5771
IS - 5
ER -
ID: 393864614