title: Mendelian randomization provides no evidence for a causal role of serum urate in increasing serum triglyceride levels.
abstract: BACKGROUND
  Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and triglyceride. The aim of this study was to test for a causal role of SU in increasing triglyceride using Mendelian randomization that accounts for unmeasured confounding.
  
  
  RESULTS
  Subjects were of European ancestry from the atherosclerosis risk in communities (n=5237) and Framingham heart (n=2971) studies. Mendelian randomization by the 2-stage least squares regression method was done with SU as the exposure, a uric acid transporter genetic risk score as instrumental variable, and triglyceride as the outcome. In ordinary linear regression, SU was significantly associated with triglyceride levels (β=2.69 mmol/L change in triglyceride per mmol/L increase in SU). However, Mendelian randomization-based estimation showed no evidence for a direct causal association of SU with triglyceride concentration-there was a nonsignificant 1.01 mmol/L decrease in triglyceride per mmol/L increase in SU attributable to the genetic risk score (P=0.21). The reverse analysis using a triglyceride genetic risk score provided evidence of a causal role for triglyceride in raising urate in men (P(Corrected)=0.018).
  
  
  CONCLUSIONS
  These data provide no evidence for a causal role for SU in raising triglyceride levels, consistent with a previous Mendelian randomization report of no association between SU and ischemic heart disease.
authors.affiliation: From the Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan (H.R.); and Department of Biochemistry, University of Otago, Dunedin, New Zealand (K.H., T.J.F., T.R.M.).
authors.forename: Humaira
authors.initials: H
authors.lastname: Rasheed
authors.affiliation: From the Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan (H.R.); and Department of Biochemistry, University of Otago, Dunedin, New Zealand (K.H., T.J.F., T.R.M.).
authors.forename: Kim
authors.initials: K
authors.lastname: Hughes
authors.affiliation: From the Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan (H.R.); and Department of Biochemistry, University of Otago, Dunedin, New Zealand (K.H., T.J.F., T.R.M.).
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Flynn
authors.affiliation: From the Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan (H.R.); and Department of Biochemistry, University of Otago, Dunedin, New Zealand (K.H., T.J.F., T.R.M.). tony.merriman@otago.ac.nz.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
mesh_terms: D001053:Apolipoproteins / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D057182:Mendelian Randomization Analysis; D027361:Organic Anion Transporters / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D014527:Uric Acid / Q000097:blood*
chemical_list: D001053:Apolipoproteins; D027361:Organic Anion Transporters; D014280:Triglycerides; C103862:urate transporter; D014527:Uric Acid
keywords: Mendelian randomization; association study; triglycerides; urate; uric acid