[show abstract][hide abstract] ABSTRACT: Background: Abdominal Aortic Aneurysm (AAA) rupture is the thirteenth leading cause of death in the U.S. and a major cause of death in the elderly. Since most AAAs are asymptomatic, mortality could be greatly reduced by determining which patients are at risk, then screening those patients prior to a rupture. Our aim was to determine which clinical and genetic risk factors are associated with AAA. Methods: This was a case- control study of patients from the Geisinger Vascular Clinic and the Geisinger MyCode Project (a biobanking project of Geisinger Clinic patients who volunteered to participate in genetic research projects). Clinical and environmental risk factor data was obtained from patient electronic medical records (EMR) and analyzed by multivariate logistic regression. In a subset of participants, we also analyzed three promising genetic polymorphisms, two from a prior genome-wide association study in this population (rs12039875, 1q41; rs7635818, 3p12.3) and one from the recent literature (rs10757278, 9p21). The genetic data was combined with the clinical data using multivariate logistic regression. Results: In the clinical analysis the number of Vascular Clinic and MyCode AAA cases totaled 722, with 11,761 controls. Adjusted OR showed a significant AAA risk for age, gender, smoking, intermittent claudication and peripheral artery disease, while body mass index (BMI) and diabetes were surprisingly protective. The genetic analysis consisted of 502 AAA cases and 295 controls from the Vascular Clinic. The GC genotype of rs7635818 showed an increased risk, but the rs12039875 AA genotype showed a significant protective effect when controlling for the clinical variables. This SNP is located in KCNK2, a gene in the potassium channel protein family. Although this gene has not previously been linked with AAA, our laboratory showed that this gene is expressed in vascular tissue. Conclusions: Our study indicates a significant elevated risk of AAA for individuals who are older, male, ever smoked, have peripheral artery disease and a GC genotype of rs7635818. Higher BMI, diabetes and the AA genotype of rs12039875 in the KCNK2 gene significantly lower AAA risk. This is one of the first studies to utilize the MyCode population in a research study and establish this population source as a valuable and convenient asset of Geisinger Health System for clinical research.