Adiposity genetic risk score modifies the association between blood lead level and body mass index

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/m ² was defined as overweight. Results: Multivariable logistic regression analysis demonstrated significant associations between BMI with each unit increase in lnBLL (b = 0.24; 95% CI, 0.08 to 0.40; P, 0.001) and each 1-point increase in BMI-GRS (b = 0.08; 95% CI, 0.05 to 0.11; P, 0.001). The causal regression coefficients of genetically determined BMI for lnBLL were 20.003 (95% CI, 20.075 to 0.070), which showed no significance. The GRS modified the association of BLL with BMI and overweight (BMI $25 kg/m ² ; 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/m ² ) were significantly modulated by BMI genetic susceptibility.