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Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome : results from IDEFICS/I.Family study and meta-analysis

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Abstract
As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p < 1.4 x 10(-4)) for 5 SNPs, which were in high LD (r(2)> 0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(beta) = 0.31, p(Wald)=1.52 x 10(-5)). We also observed a strong association of rs708272 in CETP with increased HDL (p=5.63 x 10(-40)) and decreased TRG (p=9.60 x 10(-5)) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.
Keywords
Multidisciplinary, GENOME-WIDE ASSOCIATION, FTO RS9939609 POLYMORPHISM, BODY-MASS INDEX, FAT-MASS, SUSCEPTIBILITY LOCI, VARIANT RS9939609, PHYSICAL-ACTIVITY, QUALITY-CONTROL, WEIGHT-GAIN, COMPONENTS

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MLA
Nagrani, Rajini, et al. “Common Genetic Variation in Obesity, Lipid Transfer Genes and Risk of Metabolic Syndrome : Results from IDEFICS/I.Family Study and Meta-Analysis.” SCIENTIFIC REPORTS, vol. 10, no. 1, 2020, doi:10.1038/s41598-020-64031-2.
APA
Nagrani, R., Foraita, R., Gianfagna, F., Iacoviello, L., Marild, S., Michels, N., … Marron, M. (2020). Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome : results from IDEFICS/I.Family study and meta-analysis. SCIENTIFIC REPORTS, 10(1). https://doi.org/10.1038/s41598-020-64031-2
Chicago author-date
Nagrani, Rajini, Ronja Foraita, Francesco Gianfagna, Licia Iacoviello, Staffan Marild, Nathalie Michels, Dénes Molnár, et al. 2020. “Common Genetic Variation in Obesity, Lipid Transfer Genes and Risk of Metabolic Syndrome : Results from IDEFICS/I.Family Study and Meta-Analysis.” SCIENTIFIC REPORTS 10 (1). https://doi.org/10.1038/s41598-020-64031-2.
Chicago author-date (all authors)
Nagrani, Rajini, Ronja Foraita, Francesco Gianfagna, Licia Iacoviello, Staffan Marild, Nathalie Michels, Dénes Molnár, Luis Moreno, Paola Russo, Toomas Veidebaum, Wolfgang Ahrens, and Manuela Marron. 2020. “Common Genetic Variation in Obesity, Lipid Transfer Genes and Risk of Metabolic Syndrome : Results from IDEFICS/I.Family Study and Meta-Analysis.” SCIENTIFIC REPORTS 10 (1). doi:10.1038/s41598-020-64031-2.
Vancouver
1.
Nagrani R, Foraita R, Gianfagna F, Iacoviello L, Marild S, Michels N, et al. Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome : results from IDEFICS/I.Family study and meta-analysis. SCIENTIFIC REPORTS. 2020;10(1).
IEEE
[1]
R. Nagrani et al., “Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome : results from IDEFICS/I.Family study and meta-analysis,” SCIENTIFIC REPORTS, vol. 10, no. 1, 2020.
@article{8680874,
  abstract     = {As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p < 1.4 x 10(-4)) for 5 SNPs, which were in high LD (r(2)> 0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(beta) = 0.31, p(Wald)=1.52 x 10(-5)). We also observed a strong association of rs708272 in CETP with increased HDL (p=5.63 x 10(-40)) and decreased TRG (p=9.60 x 10(-5)) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.},
  articleno    = {7189},
  author       = {Nagrani, Rajini and Foraita, Ronja and Gianfagna, Francesco and Iacoviello, Licia and Marild, Staffan and Michels, Nathalie and Molnár, Dénes and Moreno, Luis and Russo, Paola and Veidebaum, Toomas and Ahrens, Wolfgang and Marron, Manuela},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {Multidisciplinary,GENOME-WIDE ASSOCIATION,FTO RS9939609 POLYMORPHISM,BODY-MASS INDEX,FAT-MASS,SUSCEPTIBILITY LOCI,VARIANT RS9939609,PHYSICAL-ACTIVITY,QUALITY-CONTROL,WEIGHT-GAIN,COMPONENTS},
  language     = {eng},
  number       = {1},
  pages        = {14},
  title        = {Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome : results from IDEFICS/I.Family study and meta-analysis},
  url          = {http://dx.doi.org/10.1038/s41598-020-64031-2},
  volume       = {10},
  year         = {2020},
}

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