TY - JOUR AB - Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective: To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants: Genetic risk scores, composed of lipid trait-associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR, and multivariable MR method was used to test the independent association of lipids with AAA risk. The association between AAA and SNPs in loci that can act as proxies for drug targets was also assessed. Data collection took place between January 9, 2015, and January 4, 2016. Data analysis was conducted between January 4, 2015, and December 31, 2016. Exposures: Genetic elevation of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Main Outcomes and Measures: The association between genetic risk scores of lipid-associated SNPs and AAA risk, as well as the association between SNPs in lipid drug targets (HMGCR, CETP, and PCSK9) and AAA risk. Results: Up to 4914 cases and 48002 controls were included in our analysis. A 1-SD genetic elevation of LDL-C was associated with increased AAA risk (odds ratio [OR], 1.66; 95% CI, 1.41-1.96; P = 1.1 × 10-9). For HDL-C, a 1-SD increase was associated with reduced AAA risk (OR, 0.67; 95% CI, 0.55-0.82; P = 8.3 × 10-5), whereas a 1-SD increase in triglycerides was associated with increased AAA risk (OR, 1.69; 95% CI, 1.38-2.07; P = 5.2 × 10-7). In multivariable MR analysis an AU - Harrison,SC AU - Holmes,MV AU - Burgess,S AU - Asselbergs,FW AU - Jones,GT AU - Baas,AF AU - van,'t Hof FN AU - de,Bakker PIW AU - Blankensteijn,JD AU - Powell,JT AU - Saratzis,A AU - de,Borst GJ AU - Swerdlow,DI AU - van,der Graaf Y AU - van,Rij AM AU - Carey,DJ AU - Elmore,JR AU - Tromp,G AU - Kuivaniemi,H AU - Sayers,RD AU - Samani,NJ AU - Bown,MJ AU - Humphries,SE DO - 10.1001/jamacardio.2017.4293 EP - 33 PY - 2017/// SN - 2380-6583 SP - 26 TI - Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm: A Meta-analysis. T2 - JAMA Cardiology UR - http://dx.doi.org/10.1001/jamacardio.2017.4293 UR - http://hdl.handle.net/10044/1/54988 VL - 3 ER -