A genome-wide association study suggests that MAPK14 is associated with diabetic foot ulcers

Background: Diabetic foot ulcers (DFUs) are a devastating complication of diabetes. Objectives: To identify genetic contributors to the development of DFUs in the presence of peripheral neuropathy in a Scottish cohort with diabetes using a genome-wide association study. Methods: A genome-wide association approach was applied. A case was defined as a person with diabetes (type 1 or type 2) who had ever had a foot ulcer (current or previous) in at least one foot, as well as a positive monofilament test result (i.e. evidence of peripheral neuropathy) recorded in their longitudinal e-health records. A control was defined as an individual with diabetes (type 1 or type 2) who has never been recorded as having a foot ulcer in either foot but who had a positive monofilament test result recorded in either foot in their longitudinal e-health records. Results: There were 699 DFU cases and 2695 controls in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. The single-nucleotide polymorphism rs80028505 (Chr6p21·31) in MAPK14 reached genome-wide significance with a lowest P-value of 2·45 × 10 ⁻⁸ . The narrow-sense heritability of this phenotype is 0·06. Conclusions: We suggest that MAPK14 is associated with DFUs.