title: Cystatin C Is Not Causally Related to Coronary Artery Disease.
abstract: BACKGROUND
  Strong and independent associations between plasma concentration of cystatin C and risk of cardiovascular disease (CVD) suggests causal involvement of cystatin C.
  
  
  OBJECTIVE
  The aim of our study was to assess whether there is a causal relationship between plasma concentration of cystatin C and risk of coronary artery disease (CAD) using a Mendelian Randomization approach.
  
  
  METHODS
  We estimated the strength of association of plasma cystatin C on CAD risk and the strength of association of the strongest GWAS derived cystatin C SNP (rs13038305) on plasma cystatin C in the population-based Malmö Diet and Cancer Study (MDC) and thereafter the association between rs13038305 and CAD in the MDC (3200 cases of CAD and 24418 controls) and CARDIOGRAM (22233 cases of CAD and 64762 controls).
  
  
  RESULTS
  Each standard deviation (SD) increment of plasma cystatin C was associated with increased risk of CAD (OR = 1.20, 95% CI 1.07-1.34) after full adjustment. Each copy of the major allele of rs13038305 was associated with 0.34 SD higher plasma concentration of cystatin C (P<1 x 10-35), resulting in a power of >98% to detect a significant relationship between rs13038305 and CAD in MDC and CARDIOGRAM pooled. The odds ratio for CAD (per copy of the major rs13038305 allele) was 1.00 (0.94-1.07); P = 0.92 in MDC, 0.99 (0.96-1.03); P = 0.84 in CARDIOGRAM and 1.00 (0.97-1.03); P = 0.83 in MDC and CARDIOGRAM pooled.
  
  
  CONCLUSIONS
  Genetic elevation of plasma cystatin C is not related to altered risk of CAD, suggesting that there is no causal relationship between plasma cystatin C and CAD. Rather, the association between cystatin C and CAD appears to be due to the association of eGFR and CAD.
authors.affiliation: Trelleborg Hospital, Department of Internal Medicine, Trelleborg, Sweden; Institution of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Svensson-Färbom
authors.affiliation: Institution of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.affiliation: Institution of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.affiliation: Institution of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.affiliation: Institution of Clinical Sciences, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
authors.forename: Margaretha
authors.initials: M
authors.lastname: Persson
authors.affiliation: Institution of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nephrology, Skåne University Hospital, Malmö, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Christensson
authors.affiliation: Institution of Clinical Sciences, Lund University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D055316:Cystatin C