Unraveling the influence of body mass index on complex diseases in East Asians: Insights from Mendelian randomization phenome-wide association study

Medicine (Baltimore). 2025 Jun 27;104(26):e42998. doi: 10.1097/MD.0000000000042998.

Abstract

Studies on the relationship between body mass index (BMI) and different disease phenotypes have either not included systematic causal inference or have mostly focused on European populations. This highlights the importance of conducting Mendelian randomization (MR) phenome-wide association study to explore the associations between BMI and various diseases in East Asian populations. MR phenome-wide association study was utilized in this study to identify possible causal associations between BMI and 159 clinical outcomes in East Asian populations. The main statistical metrics used were odds ratio (OR) and 95% confidence interval (95% CI), employing the MR inverse variance weighted method as the principal causal inference model. Complementing these findings were analyses such as weighted median, MR-Egger, and other sensitivity analyses. Elevated BMI correlated positively with various diseases, including cardiovascular diseases like myocardial infarction (OR = 1.49; 95% CI: 1.26-1.76) and peripheral arterial disease (OR = 1.69; 95% CI: 1.34-2.13), endocrine disorders like type 1 diabetes (OR = 2.29; 95% CI: 1.39-3.77), as well as increased risk of cataracts (OR = 1.19; 95% CI: 1.09-1.31). Concurrently, BMI was associated with a reduced risk of respiratory-related diseases like pneumonia (OR = 0.75; 95% CI: 0.63-0.89), as well as cancers like breast cancer (OR = 0.67; 95% CI: 0.53-0.84) and prostate cancer (OR = 0.66; 95% CI: 0.53-0.81). BMI is causally associated with specific systemic disorders in East Asian populations. This study contributes to understanding health inequalities across various races and populations and provides insights into global health issues.

Keywords: Mendelian randomization; body mass index; causal association; complex diseases; phenome-wide association study.

MeSH terms

  • Asia, Eastern / epidemiology
  • Body Mass Index*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • East Asian People* / genetics
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Phenotype
  • Risk Factors