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The combined effect of common genetic risk variants on circulating lipoproteins is evident in childhood: A longitudinal analysis of the cardiovascular risk in Young Finns Study

Citation

Buscot, M-J and Magnussen, CG and Juonala, M and Pitkanen, N and Lehtimaki, T and Viikari, JSA and Kahonen, M and Hutri-Kahonen, N and Schork, NJ and Raitakari, OT and Thomson, RJ, The combined effect of common genetic risk variants on circulating lipoproteins is evident in childhood: A longitudinal analysis of the cardiovascular risk in Young Finns Study, PLoS ONE, 11, (1) Article e0146081. ISSN 1932-6203 (2016) [Refereed Article]


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2016 Buscot et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1371/journal.pone.0146081

Abstract

Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are modifiable risk factors for cardiovascular disease. Several genetic loci for predisposition to abnormal LDL-C, HDL-C and TG have been identified. However, it remains unclear whether these loci are consistently associated with serum lipid levels at each age or with unique developmental trajectories. Therefore, we assessed the association between genome wide association studies (GWAS) derived polygenic genetic risk scores and LDL-C, HDL-C, and triglyceride trajectories from childhood to adulthood using data available from the 27-year European 'Cardiovascular Risk in Young Finns' Study. For 2,442 participants, three weighted genetic risk scores (wGRSs) for HDL-C (38 SNPs), LDLC (14 SNPs) and triglycerides (24 SNPs) were computed and tested for association with serum lipoprotein levels measured up to 8 times between 1980 and 2011. The categorical analyses revealed no clear divergence of blood lipid trajectories over time between wGRSs categories, with participants in the lower wGRS quartiles tending to have average lipoprotein concentrations 30 to 45% lower than those in the upper-quartile wGRS beginning at age 3 years and continuing through to age 49 years (where the upper-quartile wGRS have 4-7 more risk alleles than the lower wGRS group). Continuous analyses, however, revealed a significant but moderate time-dependent genetic interaction for HDL-C levels, with the association between HDL-C and the continuous HDL-C risk score weakening slightly with age. Conversely, in males, the association between the continuous TG genetic risk score and triglycerides levels tended to be lower in childhood and become more pronounced after the age of 25 years. Although the influence of genetic factors on age-specific lipoprotein values and developmental trajectories is complex, our data show that wGRSs are highly predictive of HDL-C, LDL-C, and triglyceride levels at all ages.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Public Health and Health Services
Research Field:Epidemiology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Buscot, M-J (Miss Marie-Jeanne Buscot)
Author:Magnussen, CG (Dr Costan Magnussen)
Author:Thomson, RJ (Dr Russell Thomson)
ID Code:107487
Year Published:2016
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-03-17
Last Modified:2017-11-03
Downloads:59 View Download Statistics

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