Original Contribution Use of A Mendelian Randomization Approach to Assess the Causal Relation of g-Glutamyltransferase with Blood Pressure and Serum Insulin Levels

Elevated levels of c-glutamyltransferase (GGT) have been associated with elevated blood pressure (BP) and diabetes. However, the causality of these relations has not been addressed. The authors performed a crosssectional analysis (2003–2006) among 4,360 participants from the population-based Cohorte Lausannoise (CoLaus) Study (Lausanne, Switzerland). The rs2017869 variant of the c-glutamyltransferase 1 (GGT1) gene, which explained 1.6% of the variance in GGT levels, was used as an instrument for Mendelian randomization (MR). Sex-specific GGT quartiles were strongly associated with both systolic and diastolic BP (all P ’s < 0.0001). After multivariable adjustment, these relations were attenuated but remained significant. Using MR, the authors observed no positive association of GGT with BP (systolic: b 5.68, 95% confidence interval (CI): 11.51, 0.16 (P 1⁄4 0.06); diastolic: b 1⁄4 2.24, 95% CI: 5.98, 1.49 (P 1⁄4 0.24)). The association of GGT with insulin was also attenuated after multivariable adjustment but persisted in the fully adjusted model (b 1⁄4 0.07, 95% CI: 0.04, 0.09; P < 0.0001). Using MR, the authors also observed a positive association of GGT with insulin (b 1⁄4 0.19, 95% CI: 0.01, 0.37; P 1⁄4 0.04). In conclusion, the authors found evidence for a direct causal relation of GGT with fasting insulin but not with BP.