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The authors sought to determine whether genetically elevated HbA1c is causally associated with coronary artery disease (CAD), using Mendelian randomization. Upon including 50 HbA1c-associated variants from a GWAS study of 159,940 participants, the authors found that CAD risk was increased among those with HbA1c variants resulting in increased HbA1c levels (OR, 1.61; P=6.9 × 10−12). This finding remained significant when looking at either glycemic or erythrocytic variants alone (OR, 2.23 and 1.30, respectively).
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The authors conclude that these results suggest a causal relationship between elevated HbA1c levels and risk of CAD, which is driven by both glycemic and nonglycemic factors.