Genome-Wide Association Study of Peripheral Artery Disease

Area of Science:

• Genetics
• Cardiovascular Disease Epidemiology

Background:

• Peripheral artery disease (PAD) is a widespread condition affecting over 200 million individuals globally, carrying significant mortality and morbidity risks.
• Genetic factors play a crucial role in PAD development, necessitating further investigation into specific genomic variants.

Purpose of the Study:

• To identify novel genomic variants associated with peripheral artery disease (PAD).
• To investigate how genetic susceptibility to PAD is modified by diabetes and smoking status.

Main Methods:

• Genome-wide association analysis was performed on a large cohort of European ancestry individuals.
• Meta-analysis with existing large datasets (Million Veterans Program, UK Biobank) was conducted for replication.
• Stratified analyses were performed for individuals with and without diabetes, and for ever smokers and never smokers, including interaction analyses.

Main Results:

• Five genome-wide significant associations with PAD were identified near the LPA, CDKN2BAS1, SH2B3-PTPN11, HDAC9, and CHRNA3 loci.
• Eighteen of 19 previously reported PAD-associated variants remained significant in the meta-analysis.
• A novel variant at the CCSER1 locus was associated with PAD in individuals with diabetes (rs116405693), and a variant at the CHRNA3 locus was associated with PAD in smokers (rs12910984).

Conclusions:

• The study confirms previously identified genetic associations with PAD.
• Novel genetic variants influencing PAD susceptibility in the context of diabetes and smoking status were discovered.