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