Causal relationship between childhood obesity and non-alcoholic fatty liver disease: a Mendelian randomization study

JIANG Meichen; GUO Xian; CAO Hui

doi:10.16462/j.cnki.zhjbkz.2025.07.017

Volume 29 Issue 7

Jul. 2025

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JIANG Meichen, GUO Xian, CAO Hui. Causal relationship between childhood obesity and non-alcoholic fatty liver disease: a Mendelian randomization study[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(7): 863-868. doi: 10.16462/j.cnki.zhjbkz.2025.07.017

Citation:

JIANG Meichen, GUO Xian, CAO Hui. Causal relationship between childhood obesity and non-alcoholic fatty liver disease: a Mendelian randomization study[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2025, 29(7): 863-868. doi: 10.16462/j.cnki.zhjbkz.2025.07.017

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Causal relationship between childhood obesity and non-alcoholic fatty liver disease: a Mendelian randomization study

doi: 10.16462/j.cnki.zhjbkz.2025.07.017

1.
School of Sports Science, Beijing Sport University, Beijing 100084, China
2.
Department of Physical Education, North China Electric Power University, Beijing 100084, China

Funds:

National Key Research and Development Program of China 2018YFC200-0601

More Information

Corresponding author: GUO Xian, E-mail: guoxian@bsu.edu.cn
Received Date: 2024-11-29
Rev Recd Date: 2025-05-13

Available Online: 2025-08-11

Publish Date: 2025-07-10

Abstract

Abstract

Objective To investigate the causal relationship between genetically predicted childhood obesity and non-alcoholic fatty liver disease (NAFLD), and to provide a genetic basis for early prevention and intervention strategies of NAFLD in childhood and adulthood. Methods We conducted a two-sample Mendelian randomization (MR) study, selecting single nucleotide polymorphisms (SNPs) associated with childhood obesity from large-scale genome-wide association analyses as instrumental variables (with no linkage disequilibrium), and used NAFLD as the outcome to assess the potential causal relationship between childhood obesity and NAFLD. Results Inverse variance weighted analysis demonstrated a positive causal relationship between childhood obesity and NAFLD (OR=1.526, 95% CI: 1.298-1.793, P < 0.001). The odds ratios of weighted median method (OR=1.454, 95% CI: 1.205-1.757, P < 0.001) and MR Egger regression analysis (OR=1.257, 95% CI: 0.925-1.707, P=0.163) were both greater than 1.000, consistent with the results of inverse variance weighting analysis in direction. Conclusions Childhood obesity increases the risk of developing NAFLD, necessitating enhanced early intervention and targeted health education to reduce the risk of NAFLD in adulthood.
- Childhood obesity,
- Non-alcoholic fatty liver disease,
- Mendelian randomization

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References(27)

References

[1]	Pouwels S, Sakran N, Graham Y, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss[J]. BMC Endocr Disord, 2022, 22(1): 63. DOI: 10.1186/s12902-022-00980-1.
[2]	秦亚君, 彭海洋, 刘彦, 等. 非酒精性脂肪性肝病临床管理的研究进展[J]. 重庆医学, 2024, 53(5): 766-771. DOI: 10.3969/j.issn.1671-8348.2024.05.02. Qin YJ, Peng HY, Liu Y, et al. Research progress on clinical management of nonalcoholic fatty liver disease[J]. Chongqing Med, 2024, 53(5): 766-771. DOI: 10.3969/j.issn.1671-8348.2024.05.02.
[3]	Wei SL, Wang L, Evans PC, et al. NAFLD and NASH: etiology, targets and emerging therapies[J]. Drug Discov Today, 2024, 29(3): 103910. DOI: 10.1016/j.drudis.2024.103910.
[4]	Teng ML, Ng CH, Huang DQ, et al. Global incidence and prevalence of nonalcoholic fatty liver disease[J]. Clin Mol Hepatol, 2023, 29(Suppl): S32-S42. DOI: 10.3350/cmh.2022.0365.
[5]	Cotter TG, Rinella M. Nonalcoholic fatty liver disease 2020: the state of the disease[J]. Gastroenterology, 2020, 158(7): 1851-1864. DOI: 10.1053/j.gastro.2020.01.052.
[6]	Cuthbertson DJ, Brown E, Koskinen J, et al. Longitudinal analysis of risk of non-alcoholic fatty liver disease in adulthood[J]. Liver Int, 2019, 39(6): 1147-1154. DOI: 10.1111/liv.13993.
[7]	Draijer L, Voorhoeve M, Troelstra M, et al. A natural history study of paediatric non-alcoholic fatty liver disease over 10 years[J]. JHEP Rep, 2023, 5(5): 100685. DOI: 10.1016/j.jhepr.2023.100685.
[8]	Quek J, Chan KE, Wong ZY, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and Meta-analysis[J]. Lancet Gastroenterol Hepatol, 2023, 8(1): 20-30. DOI: 10.1016/S2468-1253(22)00317-X.
[9]	Lee EJ, Choi M, Ahn SB, et al. Prevalence of nonalcoholic fatty liver disease in pediatrics and adolescents: a systematic review and Meta-analysis[J]. World J Pediatr, 2024, 20(6): 569-580. DOI: 10.1007/s12519-024-00814-1.
[10]	Anderson EL, Howe LD, Fraser A, et al. Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: the ALSPAC study[J]. J Hepatol, 2014, 61(3): 626-632. DOI: 10.1016/j.jhep.2014.04.018.
[11]	Hu XH, Cai MX, Xiao JS, et al. Benchmarking Mendelian randomization methods for causal inference using genome-wide association study summary statistics[J]. Am J Hum Genet, 2024, 111(8): 1717-1735. DOI: 10.1016/j.ajhg.2024.06.016.
[12]	Bradfield JP, Taal HR, Timpson NJ, et al. A genome-wide association Meta-analysis identifies new childhood obesity loci[J]. Nat Genet, 2012, 44(5): 526-531. DOI: 10.1038/ng.2247.
[13]	Vogelezang S, Bradfield JP, Ahluwalia TS, et al. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits[J]. PLoS Genet, 2020, 16(10): e1008718. DOI: 10.1371/journal.pgen.1008718.
[14]	Pierce BL, Burgess S. Efficient design for mendelian randomization studies: subsample and 2-sample instrumental variable estimators[J]. Am J Epidemiol, 2013, 178(7): 1177-1184. DOI: 10.1093/aje/kwt084.
[15]	Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement[J]. J Hepatol, 2020, 73(1): 202-209. DOI: 10.1016/j.jhep.2020.03.039.
[16]	Vespoli C, Mohamed Iqbal A, Nasser Kabbany M, et al. Metabolic-associated fatty liver disease in childhood and adolescence[J]. Endocrinol Metab Clin North Am, 2023, 52(3): 417-430. DOI: 10.1016/j.ecl.2023.02.001.
[17]	Henderson GC. Plasma free fatty acid concentration as a modifiable risk factor for metabolic disease[J]. Nutrients, 2021, 13(8): 2590. DOI: 10.3390/nu13082590.
[18]	Duell PB, Welty FK, Miller M, et al. Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American heart association[J]. Arterioscler Thromb Vasc Biol, 2022, 42(6): e168-e185. DOI: 10.1161/ATV.0000000000000153.
[19]	Slevin E, Baiocchi L, Wu N, et al. Kupffer cells: inflammation pathways and cell-cell interactions in alcohol-associated liver disease[J]. Am J Pathol, 2020, 190(11): 2185-2193. DOI: 10.1016/j.ajpath.2020.08.014.
[20]	Nguyen NT, Umbaugh DS, Sanchez-Guerrero G, et al. Kupffer cells regulate liver recovery through induction of chemokine receptor CXCR2 on hepatocytes after acetaminophen overdose in mice[J]. Arch Toxicol, 2022, 96(1): 305-320. DOI: 10.1007/s00204-021-03183-0.
[21]	Ying W, Fu WX, Lee YS, et al. The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities[J]. Nat Rev Endocrinol, 2020, 16(2): 81-90. DOI: 10.1038/s41574-019-0286-3.
[22]	Gwag T, Reddy Mooli RG, Li D, et al. Macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease[J]. JHEP Rep, 2020, 3(1): 100193. DOI: 10.1016/j.jhepr.2020.100193.
[23]	Makri ES, Evripidou K, Polyzos SA. Circulating leptin in patients with nonalcoholic fatty liver disease-related liver fibrosis: a systematic review and a Meta-analysis[J]. J Gastroenterol Hepatol, 2024, 39(5): 806-817. DOI: 10.1111/jgh.16480.
[24]	Fujii H, Kawada N, Japan Study Group Of NAFLD Jsg-Nafld. The role of insulin resistance and diabetes in nonalcoholic fatty liver disease[J]. Int J Mol Sci, 2020, 21(11): 3863. DOI: 10.3390/ijms21113863.
[25]	Smith GI, Shankaran M, Yoshino M, et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease[J]. J Clin Invest, 2020, 130(3): 1453-1460. DOI: 10.1172/JCI134165.
[26]	Xu LY, Liu W, Bai FX, et al. Hepatic macrophage as a key player in fatty liver disease[J]. Front Immunol, 2021, 12: 708978. DOI: 10.3389/fimmu.2021.708978.
[27]	Geng YN, Faber KN, de Meijer VE, et al. How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?[J]. Hepatol Int, 2021, 15(1): 21-35. DOI: 10.1007/s12072-020-10121-2.