21 Background: Diabetic maculopathy is a form of diabetic retinopathy. The visual acuity of one 22 third of patients with diabetic maculopathy will be affected. The purpose of this study was to 23 identify genetic contributors of diabetic maculopathy with decreased visual acuity based on a 24 genome-wide association approach using a well-defined Scottish diabetic cohort. 25 Methods: We used linked e-health records of diabetic patients to define our cases and 26 controls. The cases in this study were defined as type 2 diabetic patients who had ever been 27 recorded in the linked e-health records as having maculopathy (observable or referable) in at 28 least one eye and whose visual acuity of the eye was recorded to have decreased between the 29 first and the last visual acuity record of that eye in the longitudinal e-health records. The 30 controls were defined as a type 2 diabetic individual who had never been diagnosed with 31 maculopathy or retinopathy in the linked e-health records. Anyone who had laser 32 photocoagulation treatment was also excluded from the controls. A standard genome-wide 33 association approach was applied. 34 Results: Overall, we identified 469 cases and 1,374 controls within the Genetics of Diabetes 35 Audit and Research in Tayside Scotland (GoDARTS) dataset. We found that the P value of 36 rs9966620 in the TTC39C gene was 4.13x10-8 , which reached genome-wide significance. 37 Conclusions: We suggest that the TTC39C gene is associated with diabetic maculopathy with 38 decreased visual acuity. This needs to be confirmed by further replication studies and functional 39 studies.