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Updated: Sep 10, 2025

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
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Age-specific childhood obesity and adult cholelithiasis: association and shared transcriptomic bases

Lihua Liu1, Lu Zhang1,2, Yiwen Liao1

  • 1Department of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

International Journal of Obesity (2005)
|August 22, 2025
PubMed

Insights

Childhood obesity, particularly at specific ages, causally links to adult gallstones. Early obesity intervention is key, with the MLXIPL gene potentially offering therapeutic targets for preventing gallstones.

Area of Science:

  • Genetics and Epidemiology
  • Public Health
  • Metabolic Disorders

Background:

  • The association between obesity and cholelithiasis (gallstones) is established.
  • The causal link between age-specific childhood obesity and adult gallstones remains unclear.
  • The biological mechanisms underlying this association are poorly understood, hindering targeted prevention.

Purpose of the Study:

  • To investigate the causal relationship between age-specific childhood body mass index (BMI) and adult cholelithiasis.
  • To explore the shared genetic and transcriptomic signals underlying this association.
  • To identify potential biological pathways for targeted interventions.

Main Methods:

  • Utilized genome-wide association study (GWAS) summary statistics for childhood BMI across 12 time points and adult cholelithiasis.
  • Employed linkage disequilibrium score regression (LDSC) for genetic correlation analysis.
  • Conducted two-sample and multivariable Mendelian randomization (MR), summary-based MR (SMR), transcriptome-wide association studies (TWAS), and Bayesian colocalization.

Main Results:

  • Significant genetic correlations were found between 11 age-specific childhood BMIs and adult cholelithiasis.
  • MR analyses confirmed causal relationships between BMI at birth and several childhood time points (8 months, 1.5, 7, and 8 years) and adult cholelithiasis.
  • The MLXIPL gene was identified as the strongest overlapping transcriptomic signal.

Conclusions:

  • Provides evidence for a causal link between childhood obesity at key developmental stages and adult gallstone formation.
  • Highlights the importance of early childhood obesity interventions.
  • Identifies MLXIPL gene expression as a potential biological pathway for therapeutic strategies against both conditions.
Abstract

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