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Extensive alterations of the whole-blood transcriptome are associated with body mass index_ results of an mRNA profiling study involving two large population-based cohorts.pdf 1,32MB
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1000 Titel
  • Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts
1000 Autor/in
  1. Homuth, Georg |
  2. Wahl, Simone |
  3. Müller, Christian |
  4. Schurmann, Claudia |
  5. Mäder, Ulrike |
  6. Blankenberg, Stefan |
  7. Carstensen, Maren |
  8. Dörr, Marcus |
  9. Endlich, Karlhans |
  10. Englbrecht, Christian |
  11. Felix, Stephan B. |
  12. Gieger, Christian |
  13. Grallert, Harald |
  14. Herder, Christian |
  15. Illig, Thomas |
  16. Kruppa, Jochen |
  17. Marzi, Carola S. |
  18. Mayerle, Julia |
  19. Meitinger, Thomas |
  20. Metspalu, Andres |
  21. Nauck, Matthias |
  22. Peters, Annette |
  23. Rathmann, Wolfgang |
  24. Reinmaa, Eva |
  25. Rettig, Rainer |
  26. Roden, Michael |
  27. Schillert, Arne |
  28. Schramm, Katharina |
  29. Steil, Leif |
  30. Strauch, Konstantin |
  31. Teumer, Alexander |
  32. Völzke, Henry |
  33. Wallaschofski, Henri |
  34. Wild, Philipp S. |
  35. Ziegler, Andreas |
  36. Völker, Uwe |
  37. Prokisch, Holger |
  38. Zeller, Tanja |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-10-15
1000 Erschienen in
1000 Quellenangabe
  • 8:65
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2015
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s12920-015-0141-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608219/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. METHODS: Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. RESULTS: Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). CONCLUSIONS: Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D.
1000 Sacherschließung
lokal Type 2 diabetes
lokal Obesity
lokal Oxidative stress
lokal Transcriptomics
lokal Insulin resistance
lokal Transcriptome-wide association study (TWAS)
lokal BMI
lokal Insulin signaling
1000 Fachgruppe
  1. Medizin |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. BMBF (German Ministry of Education and Research) |
  2. DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung – German Centre for Cardiovascular Research) |
  3. Ministry of Cultural Affairs (Germany) |
  4. Social Ministry of the Federal State of Mecklenburg-West Pomerania |
  5. Helmholtz Zentrum München – German Research Center for Environmental Health |
  6. Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW) |
  7. German Federal Ministry of Health (BMG) |
  8. German Research Foundation |
  9. DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung – German Centre for Cardiovascular Research) |
  10. Leibniz Association |
1000 Fördernummer
  1. 01ZZ9603; 01ZZ0103; 01ZZ0403; 03IS2061A; 03ZIK012; SysMBo#0315494A; 01GS0834; 01GS0823
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  3. -
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  5. -
  6. -
  7. -
  8. DFG; RA 459/2-1
  9. -
  10. -
1000 Förderprogramm
  1. Community Medicine Research net of the University of Greifswald; network ‘Greifswald Approach to Individualized Medicine (GANI_MED); BMBF Competence Network Obesity; National Genome Research Network; NGFNplus
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  3. -
  4. -
  5. -
  6. -
  7. -
  8. -
  9. -
  10. WGL Pakt für Forschung und Innovation
1000 Dateien
  1. Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer BMBF (German Ministry of Education and Research) |
    1000 Förderprogramm Community Medicine Research net of the University of Greifswald; network ‘Greifswald Approach to Individualized Medicine (GANI_MED); BMBF Competence Network Obesity; National Genome Research Network; NGFNplus
    1000 Fördernummer 01ZZ9603; 01ZZ0103; 01ZZ0403; 03IS2061A; 03ZIK012; SysMBo#0315494A; 01GS0834; 01GS0823
  2. 1000 joinedFunding-child
    1000 Förderer DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung – German Centre for Cardiovascular Research) |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Ministry of Cultural Affairs (Germany) |
    1000 Förderprogramm -
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer Social Ministry of the Federal State of Mecklenburg-West Pomerania |
    1000 Förderprogramm -
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer Helmholtz Zentrum München – German Research Center for Environmental Health |
    1000 Förderprogramm -
    1000 Fördernummer -
  6. 1000 joinedFunding-child
    1000 Förderer Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW) |
    1000 Förderprogramm -
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer German Federal Ministry of Health (BMG) |
    1000 Förderprogramm -
    1000 Fördernummer -
  8. 1000 joinedFunding-child
    1000 Förderer German Research Foundation |
    1000 Förderprogramm -
    1000 Fördernummer DFG; RA 459/2-1
  9. 1000 joinedFunding-child
    1000 Förderer DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung – German Centre for Cardiovascular Research) |
    1000 Förderprogramm -
    1000 Fördernummer -
  10. 1000 joinedFunding-child
    1000 Förderer Leibniz Association |
    1000 Förderprogramm WGL Pakt für Forschung und Innovation
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6408560.rdf
1000 Erstellt am 2018-06-27T12:17:01.950+0200
1000 Erstellt von 218
1000 beschreibt frl:6408560
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Jan 30 21:36:46 CET 2020
1000 Objekt bearb. Tue Sep 04 10:24:53 CEST 2018
1000 Vgl. frl:6408560
1000 Oai Id
  1. oai:frl.publisso.de:frl:6408560 |
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