Impact of Inherited Genetic Variants Associated With Lipid Profile, Hypertension, and Coronary Artery Disease on the Risk of Intracranial and Abdominal Aortic Aneurysms

Abstract

Epidemiological studies show that an unfavorable lipid profile and coronary artery disease (CAD) are risk traits for abdominal aortic aneurysms (AAAs) but not for intracranial aneurysms (IAs), and that hypertension is a main risk trait for IAs but not for AAAs. To evaluate these observations, we investigated single-nucleotide polymorphisms associated with serum lipid levels, hypertension, and CAD and tested their contribution to AAA and IA risk. We defined sets of single-nucleotide polymorphisms previously reported to be associated with serum lipid levels, CAD, and blood pressure. From previously collected genome-wide data, we extracted genotypes for these single-nucleotide polymorphism sets in 709 IA cases and 2692 controls and 807 AAA cases and 1905 controls (all of Dutch origin). We computed genetic scores for each individual by summing the observed number of risk alleles weighted by their previously published effect size. Using logistic regression, we tested the genetic scores for association with IAs and AAAs and found significant associations for genetic scores of total cholesterol (P=3.6×10⁻⁶), low-density lipoprotein-cholesterol (P=5.7×10⁻⁷), and CAD (P=0.0014) with AAAs and for the blood pressure score with IAs (P=0.0030). We demonstrate that genetic risk profiles of lipid factors and CAD are associated with AAAs but not with IAs, and the genetic risk profile of blood pressure is associated with IAs but not with AAAs. These findings are consistent with epidemiological observations.