Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

Abstract

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

Figure 1

The 9q33 locus. (a) The pairwise correlation structure in a 700-kb interval (123.1–123.8 Mb, NCBI B36) on chromosome 9. The upper plot shows pairwise D' for 490 common SNPs (with minor allele frequency > 5%) from the HapMap (version 22) CEU data set. The lower plot shows the corresponding r² values. (b) Estimated sex-averaged recombination rates (saRR) in centimorgans per Mb from the HapMap Phase II data. (c) Location of known genes in the region. (d) Schematic view of the association with AAA in the discovery sample sets from Iceland (blue dots) and The Netherlands (green dots), and in the two sample sets combined (red dots), for all 66 markers tested in the GWAS in the region. All panels use the same horizontal scale shown in d.