Adiposity Genetic Risk Score Modifies the Association Between Blood Lead Level and Body Mass Index

J Clin Endocrinol Metab. 2018 Nov 1;103(11):4005-4013. doi: 10.1210/jc.2018-00472.

Abstract

Context: Previous epidemiological studies had inconsistent results regarding the relationship between blood lead level (BLL) and adiposity.

Objective: We aimed to investigate the associations of BLL with body mass index (BMI) particularly using Mendelian randomization analyses and examine the interaction between obesity-predisposing genes and BLL on the associations.

Design and setting: A total of 3922 participants were enrolled from 16 sites in East China in 2014 from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (ChiCTR-ECS-14005052, www.chictr.org.cn). We calculated the weighted BMI genetic risk score (GRS) based on 29 variants that were identified and validated in East Asians. BLL was measured by atomic absorption spectrometry.

Main outcome measure: BMI was calculated, and BMI ≥25 kg/m2 was defined as overweight.

Results: Multivariable logistic regression analysis demonstrated significant associations between BMI with each unit increase in lnBLL (β = 0.24; 95% CI, 0.08 to 0.40; P < 0.001) and each 1-point increase in BMI-GRS (β = 0.08; 95% CI, 0.05 to 0.11; P < 0.001). The causal regression coefficients of genetically determined BMI for lnBLL were -0.003 (95% CI, -0.075 to 0.070), which showed no significance. The GRS modified the association of BLL with BMI and overweight (BMI ≥25 kg/m2; P for interaction = 0.031 and 0.001, respectively). Each unit of lnBLL was associated with 63% higher odds of overweight (OR 1.63; 95% CI, 1.30 to 2.05) in the highest quartile of GRS, but no significant associations were found in the lower three quartiles.

Conclusions: The associations of BLL with BMI and overweight (BMI ≥25 kg/m2) were significantly modulated by BMI genetic susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics*
  • Adult
  • Aged
  • Asian People / genetics
  • Biomarkers
  • Body Mass Index*
  • China / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lead / blood*
  • Male
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Overweight / blood
  • Overweight / diagnosis
  • Overweight / epidemiology
  • Overweight / genetics*
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Risk Factors

Substances

  • Biomarkers
  • Lead