title: Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study.
abstract: BACKGROUND
  Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished.
  
  
  METHODS
  We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011-2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFR<90ml/min/1.73m(2) and increased uACR as uACR≥30mg/g. We used the T2D_GRS as the instrumental variable (IV) to quantify the causal effect of T2D on decreased eGFR and increased uACR.
  
  
  RESULTS
  Each 1-standard deviation (SD, 3.90 points) increment in T2D_GRS was associated with decreased eGFR: odds ratio (OR)=1.18 (95% confidence interval [CI]: 1.01, 1.30). In the MR analysis, we demonstrated a causal relationship between genetically determined T2D and decreased eGFR (OR=1.47, 95% CI: 1.15, 1.88, P=0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P<0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P=0.04).
  
  
  CONCLUSIONS
  Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population.
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, 18 Life Science Park Road, Beijing 100084, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, 18 Life Science Park Road, Beijing 100084, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 100084, China. Electronic address: ymsun@capitalbio.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China. Electronic address: gning@sibs.ac.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000419:Albuminuria / Q000235:genetics*; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis / Q000379:methods; D008875:Middle Aged; D018570:Risk Assessment
keywords: Albuminuria; Causal modeling; Genetic epidemiology; Renal function; Type 2 diabetes