We are analyzing https://link.springer.com/article/10.1186/s12920-015-0141-x.

Title:
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 | BMC Medical Genomics
Description:
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.
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Keywords {🔍}

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Topics {✒️}

biotin-utp-labeled antisense-crna ship-trend/kora f4 meta-analysis ernst-moritz-arndt-university greifswald grb2-ras-raf-mek axis diet-induced obese mice z-score based p genome-wide gene expression article download pdf partner site hamburg/kiel/lübeck 2 h-ogtt glucose genome-wide association studies large population-based cohorts cis-acting enhancer sequence world-wide endemic development pdpk1-mediated tyrosine phosphorylation glutathione s-transferases μ2 significant gene-specific probes homa-ir-adjusted analysis jaccard coefficient ≥ 90th percentile array-based transcriptional profiling ship-trend study population grb2 → ras → raf → ap2k1 transcriptome-wide association study accession number e-mtab-1708 antioxidant response element partner site rhine-main erk-mediated phosphorylation cascades web-based toolkit webgestalt metafor meta-analysis package common population-relevant diseases putatively causative bmi-dependent bmc med genomics proteins/protein complexes shown insulin receptor substrate body mass index genome-wide data decreased akt-dependent phosphorylation johannes gutenberg-university mainz gene expression profiling gene-specific transcripts annotated reduced gene expression canonical ipa-pathways listed pathway primarily mediates gene expression signatures serum leptin homa-ir resulted helmholtz zentrum münchen gene regulatory networks specific gene expression gene/protein content

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         headline: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
         description: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. 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. 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). 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.
         datePublished:2015-10-15T00:00:00Z
         dateModified:2015-10-15T00:00:00Z
         pageStart:1
         pageEnd:13
         license:http://creativecommons.org/publicdomain/zero/1.0/
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         keywords:
            Transcriptomics
            Transcriptome-wide association study (TWAS)
            BMI
            Obesity
            Insulin resistance
            Type 2 diabetes
            Oxidative stress
            Insulin signaling
            Human Genetics
            Microarrays
            Gene Expression
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      headline: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
      description: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. 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. 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). 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.
      datePublished:2015-10-15T00:00:00Z
      dateModified:2015-10-15T00:00:00Z
      pageStart:1
      pageEnd:13
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12920-015-0141-x
      keywords:
         Transcriptomics
         Transcriptome-wide association study (TWAS)
         BMI
         Obesity
         Insulin resistance
         Type 2 diabetes
         Oxidative stress
         Insulin signaling
         Human Genetics
         Microarrays
         Gene Expression
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               type:PostalAddress
            type:Organization
      name:Henri Wallaschofski
      affiliation:
            name:partner site Greifswald
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
               type:PostalAddress
            type:Organization
            name:University Medicine Greifswald
            address:
               name:Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
               type:PostalAddress
            type:Organization
      name:Philipp S. Wild
      affiliation:
            name:University Medical Center of the Johannes Gutenberg-University Mainz
            address:
               name:Preventive Cardiology and Preventive Medicine, Department of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
               type:PostalAddress
            type:Organization
            name:University Medical Center of the Johannes Gutenberg-University Mainz
            address:
               name:Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Rhine-Main
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Rhine-Main, Mainz, Germany
               type:PostalAddress
            type:Organization
      name:Andreas Ziegler
      affiliation:
            name:Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein
            address:
               name:Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
               type:PostalAddress
            type:Organization
            name:Universität zu Lübeck
            address:
               name:Zentrum für Klinische Studien, Universität zu Lübeck, Lübeck, Germany
               type:PostalAddress
            type:Organization
            name:University of KwaZulu-Natal
            address:
               name:School of Statistics, Mathematics and Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa
               type:PostalAddress
            type:Organization
      name:Uwe Völker
      affiliation:
            name:University Medicine and Ernst-Moritz-Arndt-University Greifswald
            address:
               name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
               type:PostalAddress
            type:Organization
            name:partner site Greifswald
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
               type:PostalAddress
            type:Organization
      name:Holger Prokisch
      affiliation:
            name:German Research Center for Environmental Health
            address:
               name:Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Munich
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Munich, Munich, Germany
               type:PostalAddress
            type:Organization
            name:Technische Universität München
            address:
               name:Institut für Humangenetik, Technische Universität München, München, Germany
               type:PostalAddress
            type:Organization
      name:Tanja Zeller
      affiliation:
            name:Universitäres Herzzentrum Hamburg
            address:
               name:Klinik für Allgemeine und Interventionelle Kardiologie, Universitäres Herzzentrum Hamburg, Hamburg, Germany
               type:PostalAddress
            type:Organization
            name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck
            address:
               name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      name:Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:German Center for Diabetes Research (DZD), Neuherberg, Germany
      name:Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Klinik für Allgemeine und Interventionelle Kardiologie, Universitäres Herzzentrum Hamburg, Hamburg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
      name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Present Address: The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity & Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, USA
      name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      name:Klinik für Allgemeine und Interventionelle Kardiologie, Universitäres Herzzentrum Hamburg, Hamburg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
      name:Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
      name:German Center for Diabetes Research (DZD e.V.), partner site Düsseldorf, Düsseldorf, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
      name:Institute of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany
      name:German Center for Diabetes Research (DZD), Neuherberg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
      name:Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:German Center for Diabetes Research (DZD), Neuherberg, Germany
      name:Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
      name:German Center for Diabetes Research (DZD e.V.), partner site Düsseldorf, Düsseldorf, Germany
      name:Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
      name:Institute for Human Genetics, Hannover Medical School, Hannover, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
      name:Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
      name:Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:German Center for Diabetes Research (DZD), Neuherberg, Germany
      name:Department of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany
      name:Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Munich, Munich, Germany
      name:Institut für Humangenetik, Technische Universität München, München, Germany
      name:Munich Heart Alliance, Munich, Germany
      name:Estonian Genome Center, University of Tartu, Tartu, Estonia
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
      name:Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Institut für Humangenetik, Technische Universität München, München, Germany
      name:Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, University Düsseldorf, Düsseldorf, Germany
      name:Estonian Genome Center, University of Tartu, Tartu, Estonia
      name:Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
      name:Institute of Physiology, University Medicine Greifswald, Karlsburg, Germany
      name:Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
      name:German Center for Diabetes Research (DZD e.V.), partner site Düsseldorf, Düsseldorf, Germany
      name:Division of Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
      name:Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
      name:Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      name:Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
      name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
      name:Preventive Cardiology and Preventive Medicine, Department of Medicine 2, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
      name:Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Rhine-Main, Mainz, Germany
      name:Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
      name:Zentrum für Klinische Studien, Universität zu Lübeck, Lübeck, Germany
      name:School of Statistics, Mathematics and Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa
      name:Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany
      name:Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Munich, Munich, Germany
      name:Institut für Humangenetik, Technische Universität München, München, Germany
      name:Klinik für Allgemeine und Interventionelle Kardiologie, Universitäres Herzzentrum Hamburg, Hamburg, Germany
      name:DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany

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