title: Diabetes Genetic Risk Score Modifies Effect of Bisphenol A Exposure on Deterioration in Glucose Metabolism.
abstract: BACKGROUND
  Epidemiology studies showed inconsistent results regarding the relationship between bisphenol A (BPA) exposure and risk of type 2 diabetes (T2D).
  
  
  OBJECTIVE
  This study sought to prospectively investigate associations of BPA with incident T2D risk and the longitudinal changes in glycemic traits, particularly examining the interaction between gene and BPA exposure on the associations.
  
  
  METHODS
  A community-based study was conducted at baseline in 2009, including 2209 nondiabetic middle-age and elderly subjects followed for 4 y. Urinary BPA levels were measured at baseline. A genetic risk score (GRS) based on 34 T2D common variants that identified and validated in East Asians was created.
  
  
  METHODS
  Incident T2D was defined according to the 1999 World Health Organization criteria. Fasting (FPG) and 2-h post-loading plasma glucose were measured at baseline and followup.
  
  
  RESULTS
  Multivariable logistic regression analysis demonstrated no significant association of risk of incident T2D with BPA while with increase in the weighted T2D-GRS (odds ratio, 1.89; 95% confidence interval, 1.31-2.72 for each 10-point increment). Similar results were found in 4-y changes of FPG and 2-h post-loading plasma glucose. The GRS modified the effect of BPA exposure on 4-y changes in FPG (P for interaction = .01). Each 1 unit of Log_BPA was associated with 0.1 mmol/L increase in FPG (P = .007) in the highest quartile of GRS; no associations were found in the lower three quartiles of GRS.
  
  
  CONCLUSIONS
  The T2D genetic susceptibility significantly modulated the association of BPA exposure with longitudinal increase in FPG levels.
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Tiange
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Wanwan
authors.initials: W
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Shenghan
authors.initials: S
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Medical Genomics (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China; Department of Endocrine and Metabolic Diseases (Y.B., W.W., M.X., T.W., J.L., Y.X., M.D., Yu.C., D.Z., W.S., L.D., Yi.C., X.H., L.L., G.N.), Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Nutrition (L.Q.), Harvard School of Public Health, Boston, Massachusetts 02115; and Johns Hopkins University School of Medicine (S.L.), Baltimore, Maryland 21205.
authors.forename: Guang
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authors.lastname: Ning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D044466:Asian People / Q000235:genetics; D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D052244:Endocrine Disruptors / Q000009:adverse effects* / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010636:Phenols / Q000009:adverse effects* / Q000652:urine; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012306:Risk; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D052244:Endocrine Disruptors; D005947:Glucose; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds