PMID- 31472363 OWN - NLM STAT- MEDLINE DCOM- 20200424 LR - 20200424 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 178 DP - 2019 Nov TI - Exploring the associations of serum concentrations of PCBs, PCDDs, and PCDFs with walking speed in the U.S. general population: Beyond standard linear models. PG - 108666 LID - S0013-9351(19)30463-3 [pii] LID - 10.1016/j.envres.2019.108666 [doi] AB - Studies have shown that persistent organic pollutants (POPs) can have various health effects. However, little is known about the effects of multiple chemicals with possible common sources of exposure on walking speed, a proxy index reflecting lower limb neuromuscular function and physical function. We simultaneously applied multiple linear and nonlinear statistical models to explore the complex exposure-response relationship between a mixture of 22 selected POPs and walking speed. A total of 14 polychlorinated biphenyls (PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 5 polychlorinated dibenzofurans (PCDFs) were measured in the serum of participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002. Walking speed was measured during a physical examination. Linear regression (LR), least absolute shrinkage and selection operator (LASSO), and group LASSO were used to evaluate the linearity of mixtures, while restricted cubic spline (RCS) regression, random forest (RF), and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Potential confounders were adjusted in the above models. A total of 436 subjects were included in our final analysis. The results of the LR model did not identify any POP exposure that was significantly associated with walking speed. The LASSO results revealed an inverse association of one PCDD congener and two PCDF congeners with walking speed, while the group LASSO analysis identified PCDFs at the exposure level and at the group level. In the RCS analysis, two PCB congeners presented significant overall associations with walking speed. The PCB congener PCB194 showed statistically significant effects on the outcome (P = 0.01) when a permutation-based RF was used. The BKMR analysis suggested that PCBs and PCDFs (probabilities = 0.887 and 0.909, respectively) are potentially associated with walking speed. Complex statistical models, such as RCS regression, RF and BKMR models, can detect the nonlinear and nonadditive relationships between PCBs and walking speed, while LASSO and group LASSO can identify only the linear relationships between PCDFs and walking speed. Fully considering the influence of collinearity in each method during modelling can increase the comprehensiveness and reliability of conclusions in studies of multiple chemicals. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Xu, Cheng AU - Xu C AD - Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. FAU - Su, Xiaoqi AU - Su X AD - Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. FAU - Xu, Yang AU - Xu Y AD - Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. FAU - Ma, Siyu AU - Ma S AD - Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. FAU - Duan, Weiwei AU - Duan W AD - Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, China. Electronic address: passion@njmu.edu.cn. FAU - Mo, Xuming AU - Mo X AD - Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. Electronic address: mohsuming15@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190814 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Benzofurans) RN - 0 (Dibenzofurans, Polychlorinated) RN - 0 (Environmental Pollutants) RN - 0 (Polychlorinated Dibenzodioxins) RN - DFC2HB4I0K (Polychlorinated Biphenyls) SB - IM MH - Bayes Theorem MH - Benzofurans MH - Dibenzofurans, Polychlorinated/*blood MH - Environmental Exposure/*statistics & numerical data MH - Environmental Pollutants/*blood MH - Humans MH - Linear Models MH - Nutrition Surveys MH - Polychlorinated Biphenyls/*blood MH - Polychlorinated Dibenzodioxins/*blood MH - Reproducibility of Results MH - United States MH - Walking/*statistics & numerical data MH - Walking Speed OTO - NOTNLM OT - Bayesian kernel machine regression (BKMR) OT - Chemical mixture OT - NHANES OT - Restricted cubic spline (RCS) OT - Walking speed EDAT- 2019/09/01 06:00 MHDA- 2020/04/25 06:00 CRDT- 2019/09/01 06:00 PHST- 2019/06/27 00:00 [received] PHST- 2019/08/09 00:00 [revised] PHST- 2019/08/13 00:00 [accepted] PHST- 2019/09/01 06:00 [pubmed] PHST- 2020/04/25 06:00 [medline] PHST- 2019/09/01 06:00 [entrez] AID - S0013-9351(19)30463-3 [pii] AID - 10.1016/j.envres.2019.108666 [doi] PST - ppublish SO - Environ Res. 2019 Nov;178:108666. doi: 10.1016/j.envres.2019.108666. Epub 2019 Aug 14.