title: 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.
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), LDL-C (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.
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors.forename: Marie-jeanne
authors.initials: MJ
authors.lastname: Buscot
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.|Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors.forename: Costan G
authors.initials: CG
authors.lastname: Magnussen
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.|Murdoch Children Research Institute, Parkville, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Juonala
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Pitkänen
authors.affiliation: Fimlab Ltd, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Jorma S A
authors.initials: JS
authors.lastname: Viikari
authors.affiliation: Department of Clinical Physiology, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Pediatrics, University of Tampere School of Medicine and Tampere University Hospital, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.affiliation: Human Biology, The J. Craig Venter Institute, La Jolla, CA, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Thomson
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides