Genetic Support of A Causal Relationship Between Iron Status and Type 2 Diabetes: A Mendelian Randomization Study

Abstract

Context Iron overload is a known risk factor for type 2 diabetes (T2D); however, both iron overload and iron deficiency have been associated with metabolic disorders in observational studies. Objective Using Mendelian randomization (MR), we assessed how genetically predicted systemic iron status affected T2D risk. Design and Methods A two-sample MR analysis was used to obtain a causal estimate. We selected genetic variants strongly associated (P < 5×10 −8) with four biomarkers of systemic iron status from a study involving 48,972 subjects performed by the Genetics of Iron Status consortium and applied these biomarkers to the T2D case-control study (74,124 cases and 824,006 controls) performed by the Diabetes Genetics Replication and Meta-analysis consortium. The simple median, weighted median, MR-Egger, MR analysis using mixture-model, weighted allele scores, and MR based on Bayesian model averaging approaches were used for the sensitivity analysis. Results Genetically instrumented serum iron (OR: 1.07; 95% CI: 1.02–1.12), ferritin (OR: 1.19; 95% CI: 1.08–1.32), and transferrin saturation (OR: 1.06; 95% CI: 1.02–1.09) were positively associated with T2D. In contrast, genetically instrumented transferrin, a marker of reduced iron status, was inversely associated with T2D (OR: 0.91; 95% CI: 0.87–0.96). Conclusions Genetic evidence supports a causal link between increased systemic iron status and increased T2D risk. Further studies involving various ethnic backgrounds based on individual-level data and studies regarding the underlying mechanism are warranted for reducing the risk of T2D.

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The influence of LncRNA H19 polymorphic variants on susceptibility to cancer: A systematic review and updated meta-analysis of 28 case-control studies

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Nomogram and a predictive model for postoperative hemorrhage in preoperative patients of laparoscopic pancreaticoduodectomy

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