title: Diagnostic and Prognostic Metabolites Identified for Joint Symptoms in the KORA Population.
abstract: This study aims at identifying metabolites that significantly associate with self-reported joint symptoms (diagnostic) and metabolites that can predict the change from a symptom-free status to the development of self-reported joint symptoms after a 7 years period (prognostic). More than 300 metabolites were analyzed for 2246 subjects from the longitudinal study of the KORA (Cooperative Health Research in the Region of Augsburg, Germany), specifically the fourth survey S4 and its 7-year follow-up study F4. Two types of self-reported symptoms, chronic joint inflammation and worn out joints, were used for the analyses. Diagnostic analysis identified dysregulated metabolites in cases with symptoms compared with controls. Prognostic analysis identified metabolites that differentiate subjects in S4 who remained symptom-free after 7 years (F4) from those who developed any combination of symptoms. 48 metabolites were identified as nominally significantly (p < 0.05) associated with the self-reported symptoms in the diagnostic analysis, among which steroids show Bonferroni significance. 45 metabolites were identified as nominally significantly associated with developing symptoms after 7 years, among which hippurate showed Bonferroni significance. We show that metabolic profiles of self-reported joint symptoms are in line with metabolites known to associate with various forms of arthritis and suggest that future studies may benefit from that by investigating the possible use of self-reporting/questionnaire along with metabolic markers for the early referral of patients for further diagnostic workup and treatment of arthritis.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College - Qatar , Doha 24144, Qatar.|Department of Computer and Systems Engineering, Alexandria University , Alexandria 21526, Egypt.
authors.forename: Noha A
authors.initials: NA
authors.lastname: Yousri
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environment Health , 85764 Neuherberg, Germany.|German Center for Diabetes Research (DZD) , 85764 Neuherberg, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Department of Medicine, Weill Cornell Medical College - Qatar , Doha 24144, Qatar.
authors.forename: Wessam G
authors.initials: WG
authors.lastname: AlHaq
authors.affiliation: Institute of Health Economics and Health Care Management Helmholtz Zentrum , Munich, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Holle
authors.affiliation: Department of Medicine, University Hospital Munich , Campus Grosshadern, 80539 Munich, Germany.|Innenstadt, Ludwig-Maximilians University & German Center for Cardiovascular Research (DZHK) , , Munich Heart Alliance, 80337 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.affiliation: Metabolon, Inc. , Durham, North Carolina 27713, United States.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health , Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: German Center for Diabetes Research (DZD) , 85764 Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health , Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: German Center for Diabetes Research (DZD) , 85764 Neuherberg, Germany.|Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München , 85354 Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College - Qatar , Doha 24144, Qatar.|Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environment Health , 85764 Neuherberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Department of Medicine, Weill Cornell Medical College - Qatar , Doha 24144, Qatar.
authors.forename: Thurayya
authors.initials: T
authors.lastname: Arayssi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007592:Joint Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D011379:Prognosis; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: arthritis; diagnosis; joint inflammation; metabolomics; prognosis; rheumatoid arthritis