title: A causal relationship between uric acid and diabetic macrovascular disease in Chinese type 2 diabetes patients: A Mendelian randomization analysis.
abstract: BACKGROUND
  As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis.
  
  
  METHODS
  In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately.
  
  
  RESULTS
  In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR=1.068, p=0.0349; OR=1.122, p=0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β=0.203, p<0.0001; β=0.255, p<0.0001; β=0.142, p<0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR=1.184, p=0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted.
  
  
  CONCLUSIONS
  Using the uric acid-related weighted GRS as an instrumental variable for Mendelian randomization analysis, our study provided an evidence for causal relationship between uric acid and diabetic macrovascular disease in Chinese females with type 2 diabetes mellitus.
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yan
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Peng
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: He
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai 201499, China. Electronic address: alfredhc@sjtu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D003925:Diabetic Angiopathies / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000453:epidemiology; D008297:Male; D057182:Mendelian Randomization Analysis / Q000379:methods*; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014527:Uric Acid / Q000097:blood*
chemical_list: D014527:Uric Acid
keywords: Diabetic macrovascular disease; Genetic risk score; Mendelian randomization analysis; Single nucleotide polymorphism; Uric acid