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RESULTS: Genetically increased A1C was associated with higher CAD risk (odds ratio [OR] 1.61 [95% CI 1.40, 1.84] per %-unit, P = 6.9 10-12). Higher A1C was associated with increased CAD risk when using only glycemic variants (OR 2.23 [1.73, 2.89], P = 1.6 10-9) and when using only erythrocytic variants (OR 1.30 [1.08, 1.57], P = 0.004). Genetically decreased Hb, with concomitantly decreased mean corpuscular volume, was associated with higher A1C (0.30 [0.27, 0.33] %-unit, P = 2.9 10-6) per g/dL and higher CAD risk (1.18 [1.04, 1.33], P = 0.009). CONCLUSIONS: Genetic evidence supports a causal link between higher A1C and higher CAD risk. This relationship is driven not only by glycemic but also by erythrocytic, glycemia-independent factors.