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Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

TitleEvaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.
Publication TypeJournal Article
Year of Publication2018
AuthorsWeng L-C, Roetker NS, Lutsey PL, Alonso A, Guan W, Pankow JS, Folsom AR, Steffen LM, Pankratz N
Secondary AuthorsTang W
JournalPLoS One
Volume13
Issue4
Paginatione0195719
Date Published2018
ISSN1932-6203
KeywordsAged, Aged, 80 and over, Aortic Aneurysm, Abdominal, Causality, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Dyslipidemias, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Lipids, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides
Abstract

Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

DOI10.1371/journal.pone.0195719
Alternate JournalPLoS One
PubMed ID29649275
PubMed Central IDPMC5896990
Grant ListR01 HL103695 / NH / NIH HHS / United States
R01HL087641 / NH / NIH HHS / United States
R01HL59367 / NH / NIH HHS / United States
R01HL086694 / NH / NIH HHS / United States
U01HG004402 / NH / NIH HHS / United States
UL1RR025005 / NH / NIH HHS / United States