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Table 3 Mendelian randomisation studies using genetic risk scores (GRSs) to explore causality between uricaemia and cardiovascular outcomes; negative studies

From: Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options

Author year (ref) Instrumental variable (GRS) Effect on SUA variance No. of participants Population Accounted for pleiotropy Main results
Stark 2009 [73] 10 SNPs   CAD: 1473; controls: 1241 Germany No No association with CAD
Yang 2010 [66] 8 SNPs 6% >50,000 Europe and United States No Association with gout but not with BP, glucose level, CKD, CAD
Pfister 2011 [67] 8 SNPs   T2DM: 7504;
controls: 8560
  No association of the GRS SNPs with confounders No association with diabetes
Hughes 2013 [68] 5 SNPs, urate transporters 2% >70,000 ARIC and FIJS cohorts Likely to explain the observation Association with improved renal function
Rasheed 2014 [17] 5 SNPs, urate transporters 2% >70,000 ARIC and FIJS cohorts No No causal link with triglycerides; triglycerides cause hyperuricaemia
Sedaghat 2015 [69] 30 SNPs 2 mg/dL 5791 Rotterdam cohort No Negative association with SBP and DBP stronger in diuretic users
Sluijs 2015 [70] 24 loci 4% >41,500 Europeans: EOIC interact and DIAGRAM cohorts No pleiotropy except for triglycerides level No association with diabetes
Yan 2016 [65] 17 SNPs
14 excluded
  T2DM: >3200 China
Exclusion of 14 pleiotropic genes or in linkage disequilibrium Association with diabetic macro-angiopathy
Keenan 2016 [74] 28 SNPs
14 excluded
  T2DM: 65,000; controls: 68,000
CHD: 54,500; controls: 68,275
HF: 4553; controls: 19,985
IS: 14,800; controls: 19,900
South Asia
Exclusion of 14 pleiotropic genes Association with gout
No association with T2DM, CAD, stroke, HF
White 2016 [72] 31 SNPs   >166,000
>9800 CHD events
17 observational cohorts, mainly from the United Kingdom Multivariate analysis
Egger Mendelian randomisation
Multivariate OR 1–1.22; Egger OR 0.92–1.22
  1. BP blood pressure, CAD cardiovascular disease, CHD cardiac heart disease, DBP diastolic blood pressure, GRS genetic risk score, HF heart failure, OR odds ratio, SBP systolic blood pressure, SNP single nucleotide polymorphism, SUA soluble uric acid IS ischemic stroke, T2DM type 2 diabetes mellitus