title: Metabolic phenotyping for discovery of urinary biomarkers of diet, xenobiotics and blood pressure in the INTERMAP Study: an overview.
abstract: The etiopathogenesis of cardiovascular diseases (CVDs) is multifactorial. Adverse blood pressure (BP) is a major independent risk factor for epidemic CVD affecting ~40% of the adult population worldwide and resulting in significant morbidity and mortality. Metabolic phenotyping of biological fluids has proven its application in characterizing low-molecular-weight metabolites providing novel insights into gene-environmental-gut microbiome interaction in relation to a disease state. In this review, we synthesize key results from the INTERnational study of MAcro/micronutrients and blood Pressure (INTERMAP) Study, a cross-sectional epidemiologic study of 4680 men and women aged 40-59 years from Japan, the People's Republic of China, the United Kingdom and the United States. We describe the advancements we have made regarding the following: (1) analytical techniques for high-throughput metabolic phenotyping; (2) statistical analyses for biomarker identification; (3) discovery of unique food-specific biomarkers; and (4) application of metabolome-wide association studies to gain a better understanding into the molecular mechanisms of cross-cultural and regional BP differences.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
authors.forename: Queenie
authors.initials: Q
authors.lastname: Chan
authors.affiliation: Medway Metabonomics Research Group, Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, Kent, UK.|Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Ruey Leng
authors.initials: RL
authors.lastname: Loo
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.|Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Timothy M D
authors.initials: TM
authors.lastname: Ebbels
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Van Horn
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.|Institute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Daviglus
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.|MRC-NIHR National Phenome Centre, Imperial College London, London, UK.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.|Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.|MRC-NIHR National Phenome Centre, Imperial College London, London, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.|MRC-NIHR National Phenome Centre, Imperial College London, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine*; D001794:Blood Pressure / Q000502:physiology*; D004032:Diet; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis* / Q000652:urine; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D014481:United States; D015262:Xenobiotics
chemical_list: D015415:Biomarkers; D015262:Xenobiotics