Diabetes Pathology and Risk of Primary Open-Angle Glaucoma: Evaluating Causal Mechanisms by Using Genetic Information.

Diabetes Pathology and Risk of Primary Open-Angle Glaucoma: Evaluating Causal Mechanisms by Using Genetic Information. Am J Epidemiol. 2015 Nov 25; Authors: Shen L, Walter S, Melles RB, Glymour MM, Jorgenson E Abstract Although type 2 diabetes (T2D) predicts glaucoma, the potential for unmeasured confounding has hampered causal conclusions. We performed separate sample genetic instrumental variable analyses using the Genetic Epidemiology Research Study on Adult Health and Aging cohort (n = 69,685; 1995-2013) to estimate effects of T2D on primary open-angle glaucoma (POAG; 3,554 cases). Genetic instrumental variables for overall and mechanism-specific (i.e., linked to T2D via influences on adiposity, β-cell function, insulin regulation, or other metabolic processes) T2D risk were constructed by using 39 genetic polymorphisms established to predict T2D in other samples. Instrumental variable estimates indicated that T2D increased POAG risk (odds ratio = 2.53, 95% confidence interval: 1.04, 6.11). The instrumental variable for β-cell dysregulation also significantly predicted POAG (odds ratioβ-cell = 5.26, 95% confidence interval: 1.75, 15.85), even among individuals without diagnosed T2D, suggesting that metabolic dysregulation may increase POAG risk prior to T2D diagnosis. The T2D risk variant in the melatonin receptor 1B gene (MTNR1B) predicted risk of POAG independently of T2D status, indicating possible pleiotropic physiological...
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research