title: Glycerophosphocholine Metabolites and Cardiovascular Disease Risk Factors in Adolescents: A Cohort Study.
abstract: BACKGROUND
  Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia.
  
  
  METHODS
  We studied a population-based sample of 990 adolescents (12-18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m/z range. We measured VF with MRI.
  
  
  RESULTS
  We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4×10-19), blood pressure (P=7.7×10-5), and fasting triacylglycerols (P=9.0×10-5), and PC14:1/0:0 was positively associated with VF (P=3.0×10-7), fasting insulin (P=5.4×10-32), and triacylglycerols (P=1.4×10-29). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values<1.3×10-3). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs.
  
  
  CONCLUSIONS
  We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk.
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Catriona
authors.initials: C
authors.lastname: Syme
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Simon
authors.initials: S
authors.lastname: Czajkowski
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Jean
authors.initials: J
authors.lastname: Shin
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Michal
authors.initials: M
authors.lastname: Abrahamowicz
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Gabriel
authors.initials: G
authors.lastname: Leonard
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Louis
authors.initials: L
authors.lastname: Richer
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Suzanne
authors.initials: S
authors.lastname: Veillette
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Lisa
authors.initials: L
authors.lastname: Strug
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Hongbin
authors.initials: H
authors.lastname: Xu
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Graeme
authors.initials: G
authors.lastname: Taylor
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
authors.forename: Steffany
authors.initials: S
authors.lastname: Bennett
authors.affiliation: From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.). zdenka.pausova@sickkids.ca.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
mesh_terms: D000293:Adolescent; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005994:Glycerophosphates / Q000009:adverse effects*; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D005994:Glycerophosphates
keywords: adolescent; cardiovascular system; lipid metabolism; metabolomics; obesity