Finally, 4 more loci showed genome-wide significance for the association with macrovascular complications, among them rs6935464, located within the RPS6KA2 gene coding for Ribosomal Protein S6 Kinase A2, which is involved in cardiac myocyte stress responses and even considered as a therapeutic target for the prevention of heart failure [46], and rs3095447, an intron variant of Coiled-Coil Domain Containing 146 gene (CCDC146) which is also the only significant hit for ophthalmic complications in our data. The gene discussed is CCDC146; the disease is heart failure.