Epigenome-wide association study of adiposity and future risk of obesity-related diseases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-05-01

AUTHORS

Gianluca Campanella, Marc J. Gunter, Silvia Polidoro, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Giovanni Fiorito, Simonetta Guarrera, Licia Iacoviello, Ingvar A. Bergdahl, Beatrice Melin, Per Lenner, Theo M. C. M. de Kok, Panagiotis Georgiadis, Jos C. S. Kleinjans, Soterios A. Kyrtopoulos, H. Bas Bueno-de-Mesquita, Karen A. Lillycrop, Anne M. May, N. Charlotte Onland-Moret, Robert Murray, Elio Riboli, Monique Verschuren, Eiliv Lund, Nicolle Mode, Torkjel M. Sandanger, Valentina Fiano, Morena Trevisan, Giuseppe Matullo, Philippe Froguel, Paul Elliott, Paolo Vineis, Marc Chadeau-Hyam

ABSTRACT

BackgroundObesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.MethodsDNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.ResultsWe identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors.ConclusionOur results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms. More... »

PAGES

2022-2035

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  • Journal

    TITLE

    International Journal of Obesity

    ISSUE

    12

    VOLUME

    42

    Author Affiliations

  • Department of Epidemiology and Biostatistics, Imperial College London, London, UK
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France
  • Italian Institute for Genomic Medicine (IIGM), Turin, Italy
  • Fondazione IRCCS—Istituto Nazionale dei Tumori, Milan, Italy
  • Istituto per lo Studio e la Prevenzione Oncologica (ISPO Toscana), Florence, Italy
  • Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
  • Piedmont Reference Centre for Epidemiology and Cancer Prevention (CPO Piemonte), Turin, Italy
  • Cancer Registry and Histopathology Unit, Azienda Ospedaliera “Civile—M.P. Arezzo”, Ragusa, Italy
  • Department of Medical Sciences, University of Turin, Turin, Italy
  • Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli (IS), Italy
  • Department of Biobank Research, Umeå University, Umeå, Sweden
  • Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
  • Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands
  • Institute of Biology, Medicinal Chemistry, and Biotechnology, National Hellenic Research Foundation, Athens, Greece
  • Department of Social and Preventive Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • Centre for Biological Sciences, University of Southampton, Southampton, UK
  • Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
  • MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
  • Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  • Department of Community Medicine, University of Tromsø (UiT)—The Artic University of Norway, Tromsø, Norway
  • Department of Medical Sciences, Unit of Cancer Epidemiology–CERMS, University of Turin, Turin, Italy
  • Department of Genomics of Common Disease, Imperial College London, London, UK
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41366-018-0064-7

    DOI

    http://dx.doi.org/10.1038/s41366-018-0064-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1103640944

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29713043


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    33 schema:description BackgroundObesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.MethodsDNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.ResultsWe identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors.ConclusionOur results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.
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    57 biological basis
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    64 cancer
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    68 chromosome 1
    69 chronic diseases
    70 circumference
    71 clues
    72 cohort
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    74 common chronic diseases
    75 conditions
    76 contribution
    77 data
    78 discovery population
    79 disease
    80 epigenetic changes
    81 epigenome-wide association studies
    82 expression levels
    83 factors
    84 framework
    85 full-length isoform
    86 future risk
    87 gene expression levels
    88 genome-wide gene expression levels
    89 glucose
    90 high triglyceride levels
    91 high triglycerides
    92 incident breast
    93 index
    94 individuals
    95 infarction
    96 intergenic loci
    97 intermediate biomarkers
    98 intersection
    99 intersection of obesity
    100 isoforms
    101 leucocyte (PBL) DNA methylation markers
    102 levels
    103 lipid metabolism
    104 loci
    105 lower transcriptional activity
    106 markers
    107 marks
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    109 measures
    110 mechanism
    111 meta-analytical framework
    112 metabolism
    113 methylation levels
    114 methylation markers
    115 methylation marks
    116 methylation patterns
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    119 obesity
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    121 obesity-related diseases
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    123 patterns
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    129 relation
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    131 relevant subset
    132 results
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    138 triglyceride levels
    139 triglycerides
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