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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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Official URL: http://ije.oxfordjournals.org/content/early/2010/1...
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
(P3.1 10 58), 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: | Biomedical and Clinical Sciences |
| Research Group: | Cardiovascular medicine and haematology |
| Research Field: | Cardiology (incl. cardiovascular diseases) |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Magnussen, CG (Associate Professor Costan Magnussen) |
| ID Code: | 65746 |
| Year Published: | 2011 |
| Web of Science® Times Cited: | 35 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2010-12-01 |
| Last Modified: | 2022-07-07 |
| Downloads: | 0 |
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