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Conventional and Mendelian randomization analyses suggest no association between lipoprotein(a) and early atherosclerosis: the Young Finns Study

Citation

Kivimaki, M and Magnussen, CG and Juonala, M and Kahonen, M and Kettunen, J and Loo, BM and Lehtimaki, T and Viikari, J and Raitakari, OT, Conventional and Mendelian randomization analyses suggest no association between lipoprotein(a) and early atherosclerosis: the Young Finns Study , International Journal of Epidemiology, 40, (2) pp. 470-478. ISSN 0300-5771 (2011) [Refereed Article]


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The definitive publisher-authenticated version is available online at: www.oxfordjournals.org

Official URL: http://ije.oxfordjournals.org/content/early/2010/1...

DOI: doi:10.1093/ije/dyq205

Abstract

Background : Lipoprotein(a) [Lp(a)] is an established risk factor for coronary disease and stroke, but mechanisms underlying this association are unknown. We examined the association of Lp(a) with early atherosclerosis by using conventional epidemiologic analysis and a Mendelian randomization analysis. The latter utilized genetic variants that are associated with Lp(a) to estimate causal effect. Methods : A prospective population-based cohort study of 939 men and 1141 women was conducted. Lp(a) was measured repeatedly at mean ages 17 and 38 years. Measurements of carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) at mean ages 32 and 38 years were used to determine the level and 6-year progression of subclinical atherosclerosis. Lp(a)-related genetic variant, rs783147, was identified by a genome wide association analysis (P¼3.11058), and a genetic score was constructed based on 10 Lp(a)-related variants. Mendelian randomization test was performed using a two-stage instrumental variables analysis. Results: rs783147 and the genetic score were strong instruments for nonconfounded Lp(a) levels (F-statistics 269.6 and 446.0 in the first-stage instrumental variable analysis). However, Lp(a) levels were not associated with the levels of or change in IMT or FMD in any of the conventional and instrumental variables tests. The null finding was observed both with rs783147 and the genetic score as instruments and remained unchanged after adjustment for clinical characteristics, such as age, sex, HDL and LDL cholesterol, ApoB, systolic and diastolic blood pressure, diabetes and smoking. Conclusions Data from conventional and Mendelian randomization analyses provide no support for early atherogenic effects of increased Lp(a) levels.

Item Details

Item Type:Refereed Article
Keywords:Lipoprotein(a), atherosclerosis, risk factors, single-nucleotide polymorphism, Mendelian randomization
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Magnussen, CG (Dr Costan Magnussen)
ID Code:65746
Year Published:2011
Web of Science® Times Cited:25
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-12-01
Last Modified:2011-05-02
Downloads:0

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