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 | Â | 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 | Â | T2DM: 7504; controls: 8560 | Â | 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 | 2Â 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 | Â | T2DM: >3200 | China Cross-sectional | Exclusion of 14 pleiotropic genes or in linkage disequilibrium | Association with diabetic macro-angiopathy |
Keenan 2016 [74] | 28 SNPs 14 excluded | Â | T2DM: 65,000; controls: 68,000 CHD: 54,500; controls: 68,275 HF: 4553; controls: 19,985 IS: 14,800; controls: 19,900 | Europe 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 |