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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

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posted on 2023-05-18, 17:56 authored by Marie-Jeanne BuscotMarie-Jeanne Buscot, Costan Magnussen, Juonala, M, Pitkanen, N, Lehtimaki, T, Viikari, JSA, Kahonen, M, Hutri-Kahonen, N, Schork, NJ, Raitakari, OT, Russell Thomson
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.

History

Publication title

PLoS ONE

Volume

11

Article number

e0146081

Number

e0146081

Pagination

1-21

ISSN

1932-6203

Department/School

Menzies Institute for Medical Research

Publisher

Public Library of Science

Place of publication

United States

Rights statement

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

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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