Abstract 11551: Using the UK Biobank to Identify Novel Genetic Risk Factors Associated with Renal Artery Atherosclerosis

Abstract

Introduction: Atherosclerotic renal artery stenosis (ARAS) is one of the most common pathologies affecting the renal vessels and accounts for 90% of all renovascular lesions. ARAS is associated with renovascular hypertension and nephropathy. ARAS tends to be a progressive disease that has a significant impact on a patient’s overall prognosis. ARAS is likely to occur because of a complex interaction between environmental and genetic factors. We aim to utilize the UK Biobank to identify novel genetic markers associated with renal artery atherosclerosis. Methods: The UK Biobank is a prospective cohort containing clinical and genetic data gathered from over 500,000 individuals. We used Plink’s GLM options for analyzing associations between genotypes and phenotypic manifestations of the disease. We defined renal artery atherosclerosis by selecting ICD-10 code I70.1 and compared cases to age- and gender-matched controls with a case-to-control ratio of 20:1. Related individuals and those with confounding diagnoses such as coronary artery disease, ischemic cerebrovascular disease, and peripheral artery disease were excluded from the controls. Results: There are 80 and 131 instances of I70.1 as a primary or secondary diagnosis, respectively. We identified 32 variants in 22 different genes with p ≤ 1 x 10 -6 . Identified genes have a minor allele frequency ≥ 0.5%. Variants achieving genome-wide significance (p < 5 x 10 -8 ) tightly linked, representing a single haplotype on chromosome 22 near the L3MBTL2 (L3MBTL histone methyl-lysine binding protein 2; p = 3.2 x 10 -8 , OR = 8.0) and EP300-AS1 (EP300 antisense RNA 1; p = 3.5 x 10 -8 , OR = 7.9) genes. Conclusions: Genome wide analysis using ICD-10 codes as a phenotype has the potential to identify previously unknown gene loci that may contribute to an increased risk of ARAS. Future studies are warranted to confirm the association of the chromosome 22 loci to ARAS.