TY - JOUR
T1 - Adiposity genetic risk score modifies the association between blood lead level and body mass index
AU - Wang, Ningjian
AU - Lu, Meng
AU - Chen, Chi
AU - Xia, Fangzhen
AU - Han, Bing
AU - Li, Qin
AU - Cheng, Jing
AU - Chen, Yi
AU - Zhu, Chunfang
AU - Jensen, Michael D.
AU - Lu, Yingli
N1 - Publisher Copyright:
Copyright © 2018 Endocrine Society.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2018-00472
DO - 10.1210/jc.2018-00472
M3 - Article
C2 - 30202913
AN - SCOPUS:85055185412
SN - 0021-972X
VL - 103
SP - 4005
EP - 4013
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -