Genome Wide Association Study (GWAS) of Diabetic Foot Ulcers of neuropathic origin

Dansk resumé

Mennesker med diabetes har en øget risiko for amputation, der kan være mere end 25 gange større end for dem uden diabetes. Det anslås, at en underekstremitet eller en del af en underekstremitet amputeres på grund af diabetes hvert 30. sekund på verdensplan, og det er kendt, at 85 % af alle amputationer udføres på grund af et diabetisk fodsår (DFU). Diabeteskomplikationer er et resultat af genetiske og miljømæssige faktorer, og indtil dato har der kun været en Genome-wide association study (GWAS), der hvor 1 locus for DFU blev identificeret blandt voksne europæere med type 1- eller type 2-diabetes. Vi vil yderligere undersøge genetiske varianter forbundet med DFU og relaterede faktorer som fx distalt blodtryk hos et større antal europæere Vi vil anvende en GWAS meta-analyse med et case-control design omfattende flere diabetesundersøgelser med information om neuropati og DFU'er. Formålet med undersøgelsen er at identificere de underliggende risikogener og mekanistiske veje (ved hjælp af sammenfattende GWAS-statistik genereret i dette projekt) forbundet med DFU-udvikling.

Abstract

People with diabetes carry a risk of amputation that may be 25 times greater than that of people without diabetes. It is estimated that a lower limb or part of a lower limb is amputated due to diabetes every 30 seconds on a global scale, and its known that 85% of all amputations are performed due to a diabetic foot ulcer (DFU). Diabetes complications are a result of genetic and environmental factors and till date there has been just one Genome-wide association study (GWAS) that identified 1 locus for DFU among Europeans. The current study in adults with Type 1 or Type 2 diabetes will further examine genetic variants associated with DFU and related traits (distal blood pressure) in a larger number of Europeans. We here by propose a GWAS meta-analyses (case-control design) comprising multiple diabetes studies with information on neuropathy and DFUs. The aim of the study is to identify the underlying risk genes and mechanistic pathways (using summary GWAS statistics generated in the project) associated with DFU development.

Formål

To carry out a GWAS meta-analysis (case-control design) in individuals with Type1/Type2 diabetes with peripheral neuropathy and presence of foot ulcers (cases) compared to diabetes individuals with neuropathy and no foot ulcers (controls)

Studiepopulation

1. Diabetic Cases with neuropathy and foot ulcers: Persons with type 2 diabetes (T2D) having peripheral neuropathy (positive for monofilament test or Biothesiometry ≥ 25V or self-defined neuropathy eg. Questionnaire/MNsq based or ICD10 based classification of DFU), who have been diagnosed with a foot ulcer (current or previous) in at least one foot.
2. Diabetic Cases with foot ulcers: Persons with type 2 diabetes (T2D) who have been diagnosed with a foot ulcer (ever = current or previous) in at least one foot.