title: Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes.
abstract: Metabolic dysregulation underlies key metabolic risk factors—obesity, dyslipidemia, and dysglycemia.
  
  
  
  To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor changes over time.
  
  
  
  Cross-sectional—discovery samples (n = 650; age, 36–69 years) from the Framingham Heart Study (FHS) and replication samples (n = 670; age, 61–76 years) from the BioImage Study, both following a factorial design sampled from high vs low strata of body mass index, lipids, and glucose. Longitudinal—FHS participants (n = 554) with 5–7 years of follow-up for risk factor changes.
  
  
  
  Observational studies.
  
  
  
  Cross-sectional samples with or without obesity, dysglycemia, and dyslipidemia, excluding prevalent cardiovascular disease and diabetes or dyslipidemia treatment. Age- and sex-matched by group.
  
  
  
  None.
  
  
  
  Gas chromatography-mass spectrometry detected 119 plasma metabolites. Cross-sectional associations with obesity, dyslipidemia, and dysglycemia were tested in discovery, with external replication of 37 metabolites. Single- and multi-metabolite markers were tested for association with longitudinal changes in risk factors.
  
  
  
  Cross-sectional metabolite associations were identified with obesity (n = 26), dyslipidemia (n = 21), and dysglycemia (n = 11) in discovery. Glutamic acid, lactic acid, and sitosterol associated with all three risk factors in meta-analysis (P < 4.5 × 10−4). Metabolites associated with longitudinal risk factor changes were enriched for bioactive lipids. Multi-metabolite panels explained 2.5–15.3% of longitudinal changes in metabolic traits.
  
  
  
  Cross-sectional results implicated dysregulated glutamate cycling and amino acid metabolism in metabolic risk. Certain bioactive lipids were associated with risk factors cross-sectionally and over time, suggesting their upstream role in risk factor progression. Functional studies are needed to validate findings and facilitate translation into treatments or preventive measures.
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Subha
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Willinger
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: George
authors.initials: G
authors.lastname: Chen
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Peter
authors.initials: P
authors.lastname: Juhasz
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Paul
authors.initials: P
authors.lastname: Courchesne
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Li
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Pieter
authors.initials: P
authors.lastname: Muntendam
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bobeldijk-Pastorova
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Sookoian
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Pirola
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Neal
authors.initials: N
authors.lastname: Gordon
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Aram
authors.initials: A
authors.lastname: Adourian
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: Framingham Heart Study (X.Y., S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., M.G.L., D.L.), Framingham, Massachusetts 01702; Boston University Department of Mathematics and School of Public Health (X.Y., M.G.L.), Boston, Massachusetts 02118; Population Sciences Branch (S.S., C.M.W., G.C., P.C., B.H.C., S.-J.H., C.S.F., C.J.O., D.L.), Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; BG Medicine, Inc (P.J., X.L., P.M., N.G., A.A.), Waltham, Massachusetts 02451; Department of Medicine (C.S.F.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; Department of Medicine (C.J.O.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Mount Sinai School of Medicine (V.F.), New York, New York 10029; Centro Nacional de Investigaciones Cardiovasculares (V.F.), 28029 Madrid, Spain; TNO Triskelion BV, Inc (I.B.-P.), 3704 HE Zeist, The Netherlands; Institute of Medical Research A Lanari-IDIM, University of Buenos Aires (S.C.S., C.J.P.), National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires C11428, Argentina; and Boston University School of Medicine (D.L.), Boston, Massachusetts 02118.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D050171:Dyslipidemias / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012307:Risk Factors