Genetic association of lipids and lipid drug targets in abdominal aortic 1 aneurysm 2 3 4

55 Introduction 56 Risk factors for abdominal aortic aneurysm (AAA) are largely unknown and this 57 has hampered development of non-surgical treatments to alter the natural 58 history of disease. Here, we use Mendelian randomization (MR) analyses to 59 investigate the association between lipid-associated single nucleotide 60 polymorphisms and AAA. 61 Methods 62 Genetic risk scores, composed of lipid trait associated SNPs were constructed 63 and tested for their association with AAA using conventional (inverse-variance 64 weighted) MR in up to 4,914 cases and 47,912 controls across 5 studies. 65 Sensitivity analyses to account for potential genetic pleiotropy included MR66 Egger and median weighted MR, and to test the independent effect of lipids and 67 risk of AAA we used multivariable MR. Finally, we assessed the association 68 between AAA and SNPs in loci that can act as proxies for drug targets. 69 Results. 70 A 1 standard deviation (SD) genetic elevation of low-density lipoprotein 71 cholesterol (LDL-C) was associated with increased risk of AAA (odds ratio [OR] 72