1. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
- Author
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Wielscher, Matthias, Mandaviya, Pooja R, Kuehnel, Brigitte, Joehanes, Roby, Mustafa, Rima, Robinson, Oliver, Zhang, Yan, Bodinier, Barbara, Walton, Esther, Mishra, Pashupati P, Schlosser, Pascal, Wilson, Rory, Tsai, Pei-Chien, Palaniswamy, Saranya, Marioni, Riccardo E, Fiorito, Giovanni, Cugliari, Giovanni, Karhunen, Ville, Ghanbari, Mohsen, Psaty, Bruce M, Loh, Marie, Bis, Joshua C, Lehne, Benjamin, Sotoodehnia, Nona, Deary, Ian J, Chadeau-Hyam, Marc, Brody, Jennifer A, Cardona, Alexia, Selvin, Elizabeth, Smith, Alicia K, Miller, Andrew H, Torres, Mylin A, Marouli, Eirini, Gào, Xin, Van Meurs, Joyce BJ, Graf-Schindler, Johanna, Rathmann, Wolfgang, Koenig, Wolfgang, Peters, Annette, Weninger, Wolfgang, Farlik, Matthias, Zhang, Tao, Chen, Wei, Xia, Yujing, Teumer, Alexander, Nauck, Matthias, Grabe, Hans J, Doerr, Macus, Lehtimäki, Terho, Guan, Weihua, Milani, Lili, Tanaka, Toshiko, Fisher, Krista, Waite, Lindsay L, Kasela, Silva, Vineis, Paolo, Verweij, Niek, Van Der Harst, Pim, Iacoviello, Licia, Sacerdote, Carlotta, Panico, Salvatore, Krogh, Vittorio, Tumino, Rosario, Tzala, Evangelia, Matullo, Giuseppe, Hurme, Mikko A, Raitakari, Olli T, Colicino, Elena, Baccarelli, Andrea A, Kähönen, Mika, Herzig, Karl-Heinz, Li, Shengxu, BIOS Consortium, Conneely, Karen N, Kooner, Jaspal S, Köttgen, Anna, Heijmans, Bastiaan T, Deloukas, Panos, Relton, Caroline, Ong, Ken K, Bell, Jordana T, Boerwinkle, Eric, Elliott, Paul, Brenner, Hermann, Beekman, Marian, Levy, Daniel, Waldenberger, Melanie, Chambers, John C, Dehghan, Abbas, Järvelin, Marjo-Riitta, Wielscher, Matthias [0000-0003-4138-1383], Mustafa, Rima [0000-0003-2623-5337], Robinson, Oliver [0000-0002-4735-0468], Bodinier, Barbara [0000-0002-0781-3624], Walton, Esther [0000-0002-0935-2200], Schlosser, Pascal [0000-0002-8460-0462], Wilson, Rory [0000-0001-6135-3764], Palaniswamy, Saranya [0000-0003-4145-540X], Karhunen, Ville [0000-0001-6064-1588], Ghanbari, Mohsen [0000-0002-9476-7143], Psaty, Bruce M [0000-0002-7278-2190], Loh, Marie [0000-0003-3626-8466], Bis, Joshua C [0000-0002-3409-1110], Chadeau-Hyam, Marc [0000-0001-8341-5436], Brody, Jennifer A [0000-0001-8509-148X], Cardona, Alexia [0000-0002-7877-5565], Smith, Alicia K [0000-0002-8537-5156], Miller, Andrew H [0000-0001-8260-7997], Marouli, Eirini [0000-0001-6179-1609], Gào, Xin [0000-0003-0108-6961], Koenig, Wolfgang [0000-0002-2064-9603], Peters, Annette [0000-0001-6645-0985], Farlik, Matthias [0000-0003-0698-2992], Chen, Wei [0000-0003-1566-7943], Xia, Yujing [0000-0003-0850-5591], Teumer, Alexander [0000-0002-8309-094X], Nauck, Matthias [0000-0002-6678-7964], Doerr, Macus [0000-0001-7471-475X], Lehtimäki, Terho [0000-0002-2555-4427], Milani, Lili [0000-0002-5323-3102], Fisher, Krista [0000-0002-3521-0599], van der Harst, Pim [0000-0002-2713-686X], Krogh, Vittorio [0000-0003-0122-8624], Herzig, Karl-Heinz [0000-0003-4460-2604], Li, Shengxu [0000-0001-9210-7283], Köttgen, Anna [0000-0002-4671-3714], Heijmans, Bastiaan T [0000-0001-5918-0534], Deloukas, Panos [0000-0001-9251-070X], Ong, Ken K [0000-0003-4689-7530], Bell, Jordana T [0000-0002-3858-5986], Elliott, Paul [0000-0002-7511-5684], Brenner, Hermann [0000-0002-6129-1572], Beekman, Marian [0000-0003-0585-6206], Waldenberger, Melanie [0000-0003-0583-5093], Chambers, John C [0000-0003-0209-4541], Dehghan, Abbas [0000-0001-6403-016X], Järvelin, Marjo-Riitta [0000-0002-2149-0630], Apollo - University of Cambridge Repository, Maastricht Centre for Systems Biology, RS: FSE MaCSBio, Tampere University, Clinical Medicine, Department of Clinical Chemistry, BioMediTech, Department of Clinical Physiology and Nuclear Medicine, Ong, Kenneth [0000-0003-4689-7530], Internal Medicine, and Epidemiology
- Subjects
obesity ,BLOOD ,45/61 ,PREDICTION ,NF-KAPPA-B ,BIOS consortium ,General Physics and Astronomy ,General Biochemistry, Genetics and Molecular Biology ,38 ,Low grade inflammation ,MARKERS ,SDG 3 - Good Health and Well-being ,Inflammation/genetics ,risk factors ,Medicine ,Humans ,TRANSCRIPTION ,Nucleotide Motifs ,C-Reactive Protein ,CpG Islands ,DNA Methylation ,Inflammation ,EPIGENOME-WIDE ASSOCIATION ,DNA methylation ,Multidisciplinary ,business.industry ,article ,631/208/176/1988 ,692/163/2743/393 ,Cardiorespiratory fitness ,General Chemistry ,CpG Islands/genetics ,LIFETIME RISK ,GENOME ,BODY-MASS INDEX ,Immunology ,3111 Biomedicine ,C-Reactive Protein/genetics ,business ,692/499 ,DNA Methylation/genetics - Abstract
Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.
- Published
- 2022
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