title: Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates.
abstract: BACKGROUND
  The causal role of circulating sex hormone-binding globulin (SHBG) for type 2 diabetes is controversial. Information on the relations between SHBG and new biomarkers of cardiometabolic risk is scarce.
  
  
  METHODS
  We applied quantitative nuclear magnetic resonance metabolomics in three Finnish population-based cohorts to comprehensively profile circulating lipids and metabolites and study their associations with SHBG. Mendelian randomization was used to examine potential causality of SHBG on the metabolic measures and insulin resistance. Prospective associations and causal effect estimates of SHBG on type 2 diabetes were assessed via meta-analysis including summary statistics from the DIAGRAM consortium.
  
  
  RESULTS
  In cross-sectional analysis in 6475 young adults (mean age 31, 57% men), higher SHBG was linked with a more favourable cardiometabolic risk profile, including associations with lipoprotein subclasses, fatty acid composition, amino acids, ketone bodies and inflammation-linked glycoproteins. Prospective analysis of 1377 young adults with 6-year follow-up indicated that SHBG is also associated with future insulin resistance. Mendelian randomization suggested only minor, if any, causal effects of SHBG on lipid and metabolite measures and insulin resistance(n = 10,895).Causal effect estimates on type 2 diabetes for 41,439 cases and 103,870 controls indicated a causative protective role of SHBG (OR = 0.83 per 1-SD, 95% CI: 0.76, 0.91); however, effects were considerably weaker than observed in meta-analysis of prospective studies [hazard ratio (HR) = 0.47 per 1-SD, 95% CI: 0.41, 0.53].
  
  
  CONCLUSIONS
  Circulating SHBG is strongly associated with systemic metabolism and predictive for insulin resistance and diabetes. The weaker causal estimates suggest that the observational associations are partly confounded rather than conferred directly via circulating SHBG.
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Mika
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Tuulia
authors.initials: T
authors.lastname: Tynkkynen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Puukka
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland, Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland, Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland, Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland, National Institute for Health and Welfare, Helsinki, Finland, Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland, Estonian Genome Center, University of Tartu, Tartu, Estonia, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, Imperial College London, London, UK, Institute of Health Sciences & Biocenter Oulu, University of Oulu, Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol, UK and Computational Medicine, Oulu University Hospital, Oulu, Finland. Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland, NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, F
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics* / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D057182:Mendelian Randomization Analysis; D055432:Metabolomics; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; D012738:Sex Hormone-Binding Globulin
keywords: Mendelian randomization; amino acids; circulating metabolites; fatty acids; inflammation; insulin resistance; lipoproteins; sex hormone-binding globulin; type 2 diabetes