49 results on '"Dekkers, Koen F"'
Search Results
2. Oleic acid triggers metabolic rewiring of T cells poising them for T helper 9 differentiation
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Reilly, Nathalie A., Sonnet, Friederike, Dekkers, Koen F., Kwekkeboom, Joanneke C., Sinke, Lucy, Hilt, Stan, Suleiman, Hayat M., Hoeksema, Marten A., Mei, Hailiang, van Zwet, Erik W., Everts, Bart, Ioan-Facsinay, Andreea, Jukema, J. Wouter, and Heijmans, Bastiaan T.
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- 2024
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3. Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS
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Baldanzi, Gabriel, Sayols-Baixeras, Sergi, Ekblom-Bak, Elin, Ekblom, Örjan, Dekkers, Koen F., Hammar, Ulf, Nguyen, Diem, Ahmad, Shafqat, Ericson, Ulrika, Arvidsson, Daniel, Börjesson, Mats, Johanson, Peter J., Smith, J. Gustav, Bergström, Göran, Lind, Lars, Engström, Gunnar, Ärnlöv, Johan, Kennedy, Beatrice, Orho-Melander, Marju, and Fall, Tove
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- 2024
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4. Author Correction: An online atlas of human plasma metabolite signatures of gut microbiome composition
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Dekkers, Koen F., Sayols-Baixeras, Sergi, Baldanzi, Gabriel, Nowak, Christoph, Hammar, Ulf, Nguyen, Diem, Varotsis, Georgios, Brunkwall, Louise, Nielsen, Nynne, Eklund, Aron C., Bak Holm, Jacob, Nielsen, H. Bjørn, Ottosson, Filip, Lin, Yi-Ting, Ahmad, Shafqat, Lind, Lars, Sundström, Johan, Engström, Gunnar, Smith, J. Gustav, Ärnlöv, Johan, Orho-Melander, Marju, and Fall, Tove
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- 2023
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5. Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study
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Grahnemo, Louise, Nethander, Maria, Coward, Eivind, Gabrielsen, Maiken Elvestad, Sree, Satya, Billod, Jean-Marc, Sjögren, Klara, Engstrand, Lars, Dekkers, Koen F., Fall, Tove, Langhammer, Arnulf, Hveem, Kristian, and Ohlsson, Claes
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- 2023
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6. Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response
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Dekkers, Koen F., Slieker, Roderick C., Ioan-Facsinay, Andreea, van Iterson, Maarten, Ikram, M. Arfan, van Greevenbroek, Marleen M. J., Veldink, Jan H., Franke, Lude, Boomsma, Dorret I., Slagboom, P. Eline, Jukema, J. Wouter, and Heijmans, Bastiaan T.
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- 2023
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7. OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
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Baldanzi, Gabriel, Sayols-Baixeras, Sergi, Theorell-Haglöw, Jenny, Dekkers, Koen F., Hammar, Ulf, Nguyen, Diem, Lin, Yi-Ting, Ahmad, Shafqat, Holm, Jacob Bak, Nielsen, Henrik Bjørn, Brunkwall, Louise, Benedict, Christian, Cedernaes, Jonathan, Koskiniemi, Sanna, Phillipson, Mia, Lind, Lars, Sundström, Johan, Bergström, Göran, Engström, Gunnar, Smith, J. Gustav, Orho-Melander, Marju, Ärnlöv, Johan, Kennedy, Beatrice, Lindberg, Eva, and Fall, Tove
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- 2023
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8. Response by Sayols-Baixeras et al to Letter Regarding Article, “Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort”
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Sayols-Baixeras, Sergi, Dekkers, Koen F., Orho-Melander, Marju, and Fall, Tove
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- 2024
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9. Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
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Sayols-Baixeras, Sergi, Dekkers, Koen F., Baldanzi, Gabriel, Jönsson, Daniel, Hammar, Ulf, Lin, Yi-Ting, Ahmad, Shafqat, Nguyen, Diem, Varotsis, Georgios, Pita, Sara, Nielsen, Nynne, Eklund, Aron C., Holm, Jacob B., Nielsen, H. Bjørn, Ericson, Ulrika, Brunkwall, Louise, Ottosson, Filip, Larsson, Anna, Ericson, Dan, Klinge, Björn, Nilsson, Peter M., Malinovschi, Andrei, Lind, Lars, Bergström, Göran, Sundström, Johan, Ärnlöv, Johan, Engström, Gunnar, Smith, J. Gustav, Orho-Melander, Marju, and Fall, Tove
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- 2023
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10. Development of gut microbiota during the first 2 years of life
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Wernroth, Mona-Lisa, Peura, Sari, Hedman, Anna M., Hetty, Susanne, Vicenzi, Silvia, Kennedy, Beatrice, Fall, Katja, Svennblad, Bodil, Andolf, Ellika, Pershagen, Göran, Theorell-Haglöw, Jenny, Nguyen, Diem, Sayols-Baixeras, Sergi, Dekkers, Koen F., Bertilsson, Stefan, Almqvist, Catarina, Dicksved, Johan, and Fall, Tove
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- 2022
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11. An online atlas of human plasma metabolite signatures of gut microbiome composition
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Dekkers, Koen F., Sayols-Baixeras, Sergi, Baldanzi, Gabriel, Nowak, Christoph, Hammar, Ulf, Nguyen, Diem, Varotsis, Georgios, Brunkwall, Louise, Nielsen, Nynne, Eklund, Aron C., Bak Holm, Jacob, Nielsen, H. Bjørn, Ottosson, Filip, Lin, Yi-Ting, Ahmad, Shafqat, Lind, Lars, Sundström, Johan, Engström, Gunnar, Smith, J. Gustav, Ärnlöv, Johan, Orho-Melander, Marju, and Fall, Tove
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- 2022
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12. Functional genomics analysis identifies T and NK cell activation as a driver of epigenetic clock progression
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Jonkman, Thomas H., Dekkers, Koen F., Slieker, Roderick C., Grant, Crystal D., Ikram, M. Arfan, van Greevenbroek, Marleen M. J., Franke, Lude, Veldink, Jan H., Boomsma, Dorret I., Slagboom, P. Eline, Consortium, B. I. O. S., and Heijmans, Bastiaan T.
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- 2022
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13. Sociodemographic characteristics and COVID-19 testing rates : spatiotemporal patterns and impact of test accessibility in Sweden
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Kennedy, Beatrice, Varotsis, Georgios, Hammar, Ulf, Nguyen, Diem, Carrasquilla, Germán D., van Zoest, Vera, Kristiansson, Robert S., Fitipaldi, Hugo, Dekkers, Koen F., Daivadanam, Meena, Martinell, Mats, Björk, Jonas, Fall, Tove, Kennedy, Beatrice, Varotsis, Georgios, Hammar, Ulf, Nguyen, Diem, Carrasquilla, Germán D., van Zoest, Vera, Kristiansson, Robert S., Fitipaldi, Hugo, Dekkers, Koen F., Daivadanam, Meena, Martinell, Mats, Björk, Jonas, and Fall, Tove
- Abstract
Background Diagnostic testing is essential for disease surveillance and test–trace–isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates. Methods We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8–1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood. Results We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5–69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5–14 years) ranging from 0.56 (95% CI 0.47–0.67) to 0.87 (95% CI 0.80–0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10–18% decrease in inhabitants 15–29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70–105, supporting an intervention effect. Conclusions Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.
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- 2024
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14. Sociodemographic characteristics and COVID-19 testing rates:spatiotemporal patterns and impact of test accessibility in Sweden
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Kennedy, Beatrice, Varotsis, Georgios, Hammar, Ulf, Nguyen, Diem, Carrasquilla, Germán D, van Zoest, Vera, Kristiansson, Robert S, Fitipaldi, Hugo, Dekkers, Koen F, Daivadanam, Meena, Martinell, Mats, Björk, Jonas, Fall, Tove, Kennedy, Beatrice, Varotsis, Georgios, Hammar, Ulf, Nguyen, Diem, Carrasquilla, Germán D, van Zoest, Vera, Kristiansson, Robert S, Fitipaldi, Hugo, Dekkers, Koen F, Daivadanam, Meena, Martinell, Mats, Björk, Jonas, and Fall, Tove
- Abstract
BACKGROUND: Diagnostic testing is essential for disease surveillance and test-trace-isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates.METHODS: We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8-1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood.RESULTS: We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5-69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5-14 years) ranging from 0.56 (95% CI 0.47-0.67) to 0.87 (95% CI 0.80-0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10-18% decrease in inhabitants 15-29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70-105, supporting an intervention effect.CONCLUSIONS: Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.
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- 2024
15. Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals
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Mandaviya, Pooja R, Joehanes, Roby, Brody, Jennifer, Castillo-Fernandez, Juan E, Dekkers, Koen F, Do, Anh N, Graff, Mariaelisa, Hänninen, Ismo K, Tanaka, Toshiko, de Jonge, Ester AL, Kiefte-de Jong, Jessica C, Absher, Devin M, Aslibekyan, Stella, de Rijke, Yolanda B, Fornage, Myriam, Hernandez, Dena G, Hurme, Mikko A, Ikram, M Arfan, Jacques, Paul F, Justice, Anne E, Kiel, Douglas P, Lemaitre, Rozenn N, Mendelson, Michael M, Mikkilä, Vera, Moore, Ann Z, Pallister, Tess, Raitakari, Olli T, Schalkwijk, Casper G, Sha, Jin, Slagboom, Eline PE, Smith, Caren E, Stehouwer, Coen DA, Tsai, Pei-Chien, Uitterlinden, André G, van der Kallen, Carla JH, van Heemst, Diana, Arnett, Donna K, Bandinelli, Stefania, Bell, Jordana T, Heijmans, Bastiaan T, Lehtimäki, Terho, Levy, Daniel, North, Kari E, Sotoodehnia, Nona, van Greevenbroek, Marleen MJ, van Meurs, Joyce BJ, and Heil, Sandra G
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- 2019
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16. Eicosapentaenoic acid induces an anti-inflammatory transcriptomic landscape in T cells implicating a pathway independent of triglyceride lowering in cardiovascular risk reduction
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Reilly, Nathalie A., primary, Dekkers, Koen F., additional, Molenaar, Jeroen, additional, Arumugam, Sinthuja, additional, Kuipers, Thomas B., additional, Ariyurek, Yavuz, additional, Hoeksema, Marten A., additional, Jukema, J. Wouter, additional, and Heijmans, Bastiaan T., additional
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- 2024
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17. Oleic acid triggers CD4+T cells to be metabolically rewired and poised to differentiate into proinflammatory T cell subsets upon activation
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Reilly, Nathalie A., primary, Sonnet, Friederike, additional, Dekkers, Koen F., additional, Kwekkeboom, Joanneke C., additional, Sinke, Lucy, additional, Hilt, Stan, additional, Suleiman, Hayat M., additional, Hoeksema, Marten A., additional, Mei, Hailiang, additional, van Zwet, Erik W., additional, Everts, Bart, additional, Ioan-Facsinay, Andreea, additional, Jukema, J. Wouter, additional, and Heijmans, Bastiaan T., additional
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- 2024
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18. The association between the gut microbiome and 24-hour blood pressure measurements in the SCAPIS study
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Lin, Yi-Ting, primary, Sayols-Baixeras, Sergi, additional, Baldanzi, Gabriel, additional, Dekkers, Koen F, additional, Hammar, Ulf, additional, Nguyen, Diem, additional, Nielsen, Nynne, additional, Eklund, Aron C, additional, Varotsis, Georgios, additional, Holm, Jacob B, additional, Nielsen, H. Bjørn, additional, Lind, Lars, additional, Bergström, Göran, additional, Smith, J. Gustav, additional, Engström, Gunnar, additional, Ärnlöv, Johan, additional, Sundström, Johan, additional, Orho-Melander, Marju, additional, and Fall, Tove, additional
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- 2023
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19. Sociodemographic characteristics and COVID-19 testing rates: spatiotemporal patterns and impact of test accessibility in Sweden
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Kennedy, Beatrice, primary, Varotsis, Georgios, additional, Hammar, Ulf, additional, Nguyen, Diem, additional, Carrasquilla, Germán D, additional, van Zoest, Vera, additional, Kristiansson, Robert S, additional, Fitipaldi, Hugo, additional, Dekkers, Koen F, additional, Daivadanam, Meena, additional, Martinell, Mats, additional, Björk, Jonas, additional, and Fall, Tove, additional
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- 2023
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20. Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference
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Hop, Paul J., Luijk, René, Daxinger, Lucia, van Iterson, Maarten, Dekkers, Koen F., Jansen, Rick, van Meurs, Joyce B. J., ’t Hoen, Peter A. C., Ikram, M. Arfan, van Greevenbroek, Marleen M. J., Boomsma, Dorret I., Slagboom, P. Eline, Veldink, Jan H., van Zwet, Erik W., and Heijmans, Bastiaan T.
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- 2020
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21. Human monocyte-to-macrophage differentiation involves highly localized gain and loss of DNA methylation at transcription factor binding sites
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Dekkers, Koen F., Neele, Annette E., Jukema, J. Wouter, Heijmans, Bastiaan T., and de Winther, Menno P. J.
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- 2019
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22. Author Correction : An online atlas of human plasma metabolite signatures of gut microbiome composition
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Dekkers, Koen F, Sayols-Baixeras, Sergi, Baldanzi, Gabriel, Nowak, Christoph, Hammar, Ulf, Nguyen, Diem, Varotsis, Georgios, Brunkwall, Louise, Ärnlöv, Johan, Fall, Tove, Dekkers, Koen F, Sayols-Baixeras, Sergi, Baldanzi, Gabriel, Nowak, Christoph, Hammar, Ulf, Nguyen, Diem, Varotsis, Georgios, Brunkwall, Louise, Ärnlöv, Johan, and Fall, Tove
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- 2023
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23. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
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Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J.M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adragni, Kofi, Allesøe, Rosa Lundbye L., Artati, Anna A., Arumugam, Manimozhiyan, Atabaki-Pasdar, Naeimeh, Baltauss, Tania, Banasik, Karina, Barnett, Anna L., Baum, Patrick, Bell, Jimmy D., Beulens, Joline W., Bianzano, Susanna B., Bizzotto, Roberto, Bonnefond, Amelie, Cabrelli, Louise, Dale, Matilda, Dawed, Adem Y., de Preville, Nathalie, Dekkers, Koen F., Deshmukh, Harshal A., Dings, Christiane, Donnelly, Louise, Dutta, Avirup, Ehrhardt, Beate, Engelbrechtsen, Line, Eriksen, Rebeca, Fan, Yong, Ferrer, Jorge, Fitipaldi, Hugo, Forman, Annemette, Fritsche, Andreas, Froguel, Philippe, Gassenhuber, Johann, Gough, Stephen, Graefe-Mody, Ulrike, Grempler, Rolf, Groeneveld, Lenka, Groop, Leif, Gudmundsdóttir, Valborg, Gupta, Ramneek, Hennige, Anita M.H., Hill, Anita V., Holl, Reinhard W., Hudson, Michelle, Jacobsen, Ulrik Plesner, Jennison, Christopher, Johansen, Joachim, Jonsson, Anna, Karaderi, Tugce, Kaye, Jane, Kennedy, Gwen, Klintenberg, Maria, Kuulasmaa, Teemu, Lehr, Thorsten, Loftus, Heather, Lundgaard, Agnete Troen T., Mazzoni, Gianluca, McRobert, Nicky, McVittie, Ian, Nice, Rachel, Nicolay, Claudia, Nijpels, Giel, Palmer, Colin N., Pedersen, Helle K., Perry, Mandy H., Pomares-Millan, Hugo, Prehn, Cornelia P., Ramisch, Anna, Rasmussen, Simon, Robertson, Neil, Rodriquez, Marianne, Sackett, Peter, Scherer, Nina, Shah, Nisha, Sihinevich, Iryna, Slieker, Roderick C., Sondertoft, Nadja B., Steckel-Hamann, Birgit, Thomas, Melissa K., Thomas, Cecilia Engel E., Thomas, Elizabeth Louise L., Thorand, Barbara, Thorne, Claire E., Tillner, Joachim, Tura, Andrea, Uhlen, Mathias, van Leeuwen, Nienke, van Oort, Sabine, Verkindt, Helene, Vogt, Josef, Wad Sackett, Peter W., Wesolowska-Andersen, Agata, Whitcher, Brandon, White, Margaret W., Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., Viñuela, Ana, Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J.M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adragni, Kofi, Allesøe, Rosa Lundbye L., Artati, Anna A., Arumugam, Manimozhiyan, Atabaki-Pasdar, Naeimeh, Baltauss, Tania, Banasik, Karina, Barnett, Anna L., Baum, Patrick, Bell, Jimmy D., Beulens, Joline W., Bianzano, Susanna B., Bizzotto, Roberto, Bonnefond, Amelie, Cabrelli, Louise, Dale, Matilda, Dawed, Adem Y., de Preville, Nathalie, Dekkers, Koen F., Deshmukh, Harshal A., Dings, Christiane, Donnelly, Louise, Dutta, Avirup, Ehrhardt, Beate, Engelbrechtsen, Line, Eriksen, Rebeca, Fan, Yong, Ferrer, Jorge, Fitipaldi, Hugo, Forman, Annemette, Fritsche, Andreas, Froguel, Philippe, Gassenhuber, Johann, Gough, Stephen, Graefe-Mody, Ulrike, Grempler, Rolf, Groeneveld, Lenka, Groop, Leif, Gudmundsdóttir, Valborg, Gupta, Ramneek, Hennige, Anita M.H., Hill, Anita V., Holl, Reinhard W., Hudson, Michelle, Jacobsen, Ulrik Plesner, Jennison, Christopher, Johansen, Joachim, Jonsson, Anna, Karaderi, Tugce, Kaye, Jane, Kennedy, Gwen, Klintenberg, Maria, Kuulasmaa, Teemu, Lehr, Thorsten, Loftus, Heather, Lundgaard, Agnete Troen T., Mazzoni, Gianluca, McRobert, Nicky, McVittie, Ian, Nice, Rachel, Nicolay, Claudia, Nijpels, Giel, Palmer, Colin N., Pedersen, Helle K., Perry, Mandy H., Pomares-Millan, Hugo, Prehn, Cornelia P., Ramisch, Anna, Rasmussen, Simon, Robertson, Neil, Rodriquez, Marianne, Sackett, Peter, Scherer, Nina, Shah, Nisha, Sihinevich, Iryna, Slieker, Roderick C., Sondertoft, Nadja B., Steckel-Hamann, Birgit, Thomas, Melissa K., Thomas, Cecilia Engel E., Thomas, Elizabeth Louise L., Thorand, Barbara, Thorne, Claire E., Tillner, Joachim, Tura, Andrea, Uhlen, Mathias, van Leeuwen, Nienke, van Oort, Sabine, Verkindt, Helene, Vogt, Josef, Wad Sackett, Peter W., Wesolowska-Andersen, Agata, Whitcher, Brandon, White, Margaret W., Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., and Viñuela, Ana
- Abstract
We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.
- Published
- 2023
24. A Swedish dietary guideline index, gut microbial α-diversity and prevalence of metabolic syndrome -- observations in the Swedish CArdioPulmonary bioImage Study (SCAPIS).
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Ericson, Ulrika, Hellstrand, Sophie, Larsson, Anna, Miari, Mariam, Baixeras, Sergi Sayols, Dekkers, Koen F., Bergström, Göran, Malinovschi, Andrei, Engström, Gunnar, Ärnlöv, Johan, Fall, Tove, and Orho-Melander, Marju
- Subjects
NUTRITION policy ,PATIENT compliance ,STATISTICAL models ,RESEARCH funding ,GUT microbiome ,SEX distribution ,DESCRIPTIVE statistics ,BACTERIA ,EXPERIMENTAL design ,METABOLIC syndrome ,RESEARCH methodology ,SEQUENCE analysis ,GENOMES - Abstract
Background: Metabolic syndrome (MetS) is characterized by coexisting risk factors for type 2 diabetes and cardiovascular disease. Diet is of importance in their aetiology, and gut microbiota (GM) may constitute a link between diet and metabolic health. Understanding the interplay between diet and GM could contribute novel insights for future dietary guidelines, and aid in preventive actions to motivate adherence to dietary guidelines. Objective: We intended to create a Swedish dietary guideline index (SweDGI) measuring adherence to 12 Swedish dietary guidelines and examine whether SweDGI and its components are associated with GM α-diversity (Shannon index) and prevalent MetS, and if the association between the Shannon index and MetS differs depending on SweDGI. Design: SweDGI was based on food-frequency data assessed 2014--2018 in 10,396 diabetes-free participants from the Malmö and Uppsala-sites of the Swedish CArdioPulmonary bioImage Study (SCAPIS) (50--64 y, 53% women). We estimated the Shannon index from shotgun metagenomic sequencing-data to assess microbial richness and evenness. We used a general linear model to examine cross-sectional SweDGI-Shannon associations and logistic regression for associations with MetS. Results: Most guidelines were followed by less than half of the participants. Men showed poorer adherence. Higher SweDGI was linked to higher Shannon index (P-trend across five SweDGI-groups = 1.7 x 10
-12 ). Most guidelines contributed to this observation. Higher SweDGI and Shannon index were associated with lower MetSprevalence, where the lowest prevalence was observed among those with both high SweDGI and high Shannon index (odds ratio:0.43; 95% confidence interval:0.35, 0.52). Both the Shannon index and SweDGI were associated with MetS, independently of the level of the other factor (P-interaction = 0.82). Conclusions: We created a new index to comprehensively reflect adherence to the Swedish dietary guidelines in sub-cohorts within the large multicentre SCAPIS study. Better adherence was associated with a richer and more even GM and lower prevalence of MetS. The inverse association between the Shannon index and MetS was consistent at different levels of adherence to dietary guidelines. [ABSTRACT FROM AUTHOR]- Published
- 2024
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25. Genome-wide identification of directed gene networks using large-scale population genomics data
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Luijk, René, Dekkers, Koen F., van Iterson, Maarten, Arindrarto, Wibowo, Claringbould, Annique, Hop, Paul, Boomsma, Dorret I., van Duijn, Cornelia M., van Greevenbroek, Marleen M. J., Veldink, Jan H., Wijmenga, Cisca, Franke, Lude, ’t Hoen, Peter A. C., Jansen, Rick, van Meurs, Joyce, Mei, Hailiang, Slagboom, P. Eline, Heijmans, Bastiaan T., van Zwet, Erik W., and BIOS (Biobank-based Integrative Omics Study) Consortium
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- 2018
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26. The metabolomic profile associated with clustering of cardiovascular risk factors—A multi-sample evaluation
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Lind, Lars, primary, Sundström, Johan, additional, Elmståhl, Sölve, additional, Dekkers, Koen F., additional, Smith, J. Gustav, additional, Engström, Gunnar, additional, Fall, Tove, additional, and Ärnlöv, Johan, additional
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- 2022
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27. DNA methylation signatures of educational attainment
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van Dongen, Jenny, Bonder, Marc Jan, Dekkers, Koen F., Nivard, Michel G., van Iterson, Maarten, Willemsen, Gonneke, Beekman, Marian, van der Spek, Ashley, van Meurs, Joyce B. J., Franke, Lude, Heijmans, Bastiaan T., van Duijn, Cornelia M., Slagboom, P. Eline, Boomsma, Dorret I., and BIOS consortium
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- 2018
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28. The metabolomic profile associated with clustering of cardiovascular risk factors-A multi-sample evaluation
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Lind, Lars, Sundström, Johan, Elmståhl, Sölve, Dekkers, Koen F, Smith, J Gustav, Engström, Gunnar, Fall, Tove, Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Elmståhl, Sölve, Dekkers, Koen F, Smith, J Gustav, Engström, Gunnar, Fall, Tove, and Ärnlöv, Johan
- Abstract
BACKGROUND: A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to find a metabolic profile common for all five components of MetS. METHODS AND FINDINGS: 791 annotated non-xenobiotic metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in five different population-based samples (Discovery samples: EpiHealth, n = 2342 and SCAPIS-Uppsala, n = 4985. Replication sample: SCAPIS-Malmö, n = 3978, Characterization samples: PIVUS, n = 604 and POEM, n = 501). MetS was defined by the NCEP/consensus criteria. Fifteen metabolites were related to all five components of MetS (blood pressure, waist circumference, glucose, HDL-cholesterol and triglycerides) at a false discovery rate of <0.05 with adjustments for BMI and several life-style factors. They represented different metabolic classes, such as amino acids, simple carbohydrates, androgenic steroids, corticosteroids, co-factors and vitamins, ceramides, carnitines, fatty acids, phospholipids and metabolonic lactone sulfate. All 15 metabolites were related to insulin sensitivity (Matsuda index) in POEM, but only Palmitoyl-oleoyl-GPE (16:0/18:1), a glycerophospholipid, was related to incident cardiovascular disease over 8.6 years follow-up in the EpiHealth sample following adjustment for cardiovascular risk factors (HR 1.32 for a SD change, 95%CI 1.07-1.63). CONCLUSION: A complex metabolic profile was related to all cardiovascular risk factors included in MetS independently of BMI. This profile was also related to insulin sensitivity, which provide further support for the importance of insulin sensitivity as an important underlying mechanism in the clustering of cardiovascular risk factors.
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- 2022
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29. Streptococcusspecies abundance in the gut is linked to subclinical coronary atherosclerosis in 8973 participants from the SCAPIS cohort
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Sayols-Baixeras, Sergi, primary, Dekkers, Koen F., additional, Baldanzi, Gabriel, additional, Jönsson, Daniel, additional, Hammar, Ulf, additional, Lin, Yi-Ting, additional, Ahmad, Shafqat, additional, Nguyen, Diem, additional, Varotsis, Georgios, additional, Pita, Sara, additional, Nielsen, Nynne, additional, Eklund, Aron C., additional, Holm, Jacob Bak, additional, Nielsen, H. Bjørn, additional, Ericson, Ulrika, additional, Brunkwall, Louise, additional, Ottosson, Filip, additional, Larsson, Anna, additional, Ericson, Dan, additional, Klinge, Björn, additional, Nilsson, Peter M., additional, Malinovschi, Andrei, additional, Lind, Lars, additional, Bergström, Göran, additional, Sundström, Johan, additional, Ärnlöv, Johan, additional, Engström, Gunnar, additional, Smith, J. Gustav, additional, Orho-Melander, Marju, additional, and Fall, Tove, additional
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- 2022
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30. Additional file 5 of Functional genomics analysis identifies T and NK cell activation as a driver of epigenetic clock progression
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Jonkman, Thomas H., Dekkers, Koen F., Slieker, Roderick C., Grant, Crystal D., Ikram, M. Arfan, van Greevenbroek, Marleen M. J., Franke, Lude, Veldink, Jan H., Boomsma, Dorret I., Slagboom, P. Eline, Consortium, B. I. O. S., and Heijmans, Bastiaan T.
- Abstract
Additional file 5. Review history.
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- 2022
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31. The multifaceted interplay between lipids and epigenetics
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Dekkers, Koen F., Slagboom, P. Eline, Jukema, J. Wouter, and Heijmans, Bastiaan T.
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- 2016
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32. An online atlas of human plasma metabolite signatures of gut microbiome composition
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Dekkers, Koen F., primary, Sayols-Baixeras, Sergi, additional, Baldanzi, Gabriel, additional, Nowak, Christoph, additional, Hammar, Ulf, additional, Nguyen, Diem, additional, Varotsis, Georgios, additional, Brunkwall, Louise, additional, Nielsen, Nynne, additional, Eklund, Aron C., additional, Holm, Jacob Bak, additional, Nielsen, H. Bjørn, additional, Ottosson, Filip, additional, Lin, Yi-Ting, additional, Ahmad, Shafqat, additional, Lind, Lars, additional, Sundström, Johan, additional, Engström, Gunnar, additional, Smith, J. Gustav, additional, Ärnlöv, Johan, additional, Orho-Melander, Marju, additional, and Fall, Tove, additional
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- 2021
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33. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
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Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Alfredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, Cilla, Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalitha, Mandaviya, Pooja, Hottenga, Jouke Jan, Bernard, Manon, Perry, John R.B., Felix, Janine F., Rivadeneira, Fernando, Tiemeier, Henning, Uitterlinden, André G., Jaddoe, Vincent W.V., Hansen, Torben, Ikram, M. Arfan, Bell, Jordana T., van Meurs, Joyce, van IJzendoorn, Marinus, Mill, Jonathan, Relton, Caroline L., Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Alfredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, Cilla, Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalitha, Mandaviya, Pooja, Hottenga, Jouke Jan, Bernard, Manon, Perry, John R.B., Felix, Janine F., Rivadeneira, Fernando, Tiemeier, Henning, Uitterlinden, André G., Jaddoe, Vincent W.V., Hansen, Torben, Ikram, M. Arfan, Bell, Jordana T., van Meurs, Joyce, van IJzendoorn, Marinus, Mill, Jonathan, and Relton, Caroline L.
- Abstract
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
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- 2021
34. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
- Author
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UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, Alarcón-Riquelme, Marta, UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, and Alarcón-Riquelme, Marta
- Abstract
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
- Published
- 2021
35. Sex-dependent gene regulation of human atherosclerotic plaques by DNA methylation and transcriptome integration points to smooth muscle cell involvement in women
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Hartman, Robin J. G., primary, Siemelink, Marten A., additional, Haitjema, Saskia, additional, Dekkers, Koen F., additional, Slenders, Lotte, additional, Boltjes, Arjan, additional, Mokry, Michal, additional, Timmerman, Nathalie, additional, de Borst, Gert J., additional, Heijmans, Bastiaan T., additional, Asselbergs, Folkert W., additional, Pasterkamp, Gerard, additional, van der Laan, Sander W., additional, and den Ruijter, Hester M., additional
- Published
- 2021
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36. SOCIODEMOGRAPHIC CHARACTERISTICS AND COVID-19 TESTING RATES: SPATIO-TEMPORAL PATTERNS AND IMPACT OF TEST ACCESSIBILITY IN SWEDEN
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Kennedy, Beatrice, primary, Varotsis, Georgios, additional, Hammar, Ulf, additional, Nguyen, Diem, additional, Carrasquilla, Germán D., additional, van Zoest, Vera, additional, Kristiansson, Robert S., additional, Fitipaldi, Hugo, additional, Dekkers, Koen F., additional, Daivadanam, Meena, additional, Martinell, Mats, additional, Björk, Jonas, additional, and Fall, Tove, additional
- Published
- 2020
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37. Additional file 4 of Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference
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Hop, Paul J., Luijk, René, Daxinger, Lucia, Iterson, Maarten Van, Dekkers, Koen F., Jansen, Rick, Meurs, Joyce B. J. Van, Peter A. C. ’T Hoen, M. Arfan Ikram, Greevenbroek, Marleen M. J. Van, Dorret I. Boomsma, P. Eline Slagboom, Veldink, Jan H., Zwet, Erik W. Van, and Heijmans, Bastiaan T.
- Abstract
Additional file 4: Table S6. Comparison with previous trans-methylation QTL studies in blood. Fig. S1. Test-statistics before and after adjustment for SNPs associated with white blood cell counts. Fig. S2. Power analyses. Fig. S3. Explained variance of genetic instruments for TFs and non-TFs. Fig. S4. Volcano plots for DNMT3A and DNMT1. Fig. S5. Volcano plots for CDCA7 and CDCA7L. Fig. S6. Increase in statistical power with larger sample sizes. Fig. S7. Diagram showing the presumed relations between genetic instruments, expression and DNA methylation.
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- 2020
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38. Additional file 19 of Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference
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Hop, Paul J., Luijk, René, Daxinger, Lucia, Iterson, Maarten Van, Dekkers, Koen F., Jansen, Rick, Meurs, Joyce B. J. Van, Peter A. C. ’T Hoen, M. Arfan Ikram, Greevenbroek, Marleen M. J. Van, Dorret I. Boomsma, P. Eline Slagboom, Veldink, Jan H., Zwet, Erik W. Van, and Heijmans, Bastiaan T.
- Abstract
Additional file 19. Review history.
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- 2020
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39. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood
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Tobi, Elmar W., Slieker, Roderick C., Luijk, René, Dekkers, Koen F., Stein, Aryeh D., Xu, Kate M., Slagboom, P.E., Van Zwet, Erik W., Lumey, L.H., Heijmans, Bastiaan T., T'Hoen, Peter A., Pool, René, Van Greevenbroek, Marleen M., Stehouwer, Coen D., Van Der Kallen, Carla J., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan H., Van Den Berg, Leonard H., Van Duijn, Cornelia M., Hofman, Albert, Uitterlinden, André G., Jhamai, P.M., Verbiest, Michael, Verkerk, Marijn, Van Der Breggen, Ruud, Van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, Bot, Jan, Zhernakova, Dasha V., Van 't Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Jan Bonder, Marc, Van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., Isaacs, Aaron, Franke, Lude, Epidemiology and Data Science, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, Laboratory Medicine, RS-Theme Biopsychology of Learning, and Department FEEEL
- Subjects
0301 basic medicine ,BLOOD ,Physiology ,Genome-wide association study ,Diseases and Disorders ,Body Mass Index ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Medicine ,MATERNAL SMOKING ,EPIGENETIC REGULATION ,Research Articles ,2. Zero hunger ,Multidisciplinary ,SciAdv r-articles ,Middle Aged ,DATA RESOURCE ,EPIGENETIC EPIDEMIOLOGY ,Metabolism disorder ,030220 oncology & carcinogenesis ,Prenatal Exposure Delayed Effects ,DNA methylation ,Female ,TXNIP ,Research Article ,Adult ,FAMINE EXPOSURE ,IN-UTERO ,HUNGER WINTER FAMILIES ,03 medical and health sciences ,BMI ,AGE ,SDG 3 - Good Health and Well-being ,Metabolic Diseases ,DUTCH FAMINE ,Life Science ,Humans ,Epigenetics ,EXPOSURE ,Triglycerides ,EPIGENOME-WIDE ASSOCIATION ,Global Nutrition ,Wereldvoeding ,business.industry ,dNaM ,Human Genetics ,DNA Methylation ,medicine.disease ,GENE ,BODY-MASS INDEX ,030104 developmental biology ,Starvation ,business ,Body mass index ,Genome-Wide Association Study - Abstract
DNA methylation mediates the association of prenatal famine exposure with higher adult BMI and serum triglyceride levels., Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis. DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing β cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-term metabolic health. The specific mechanism awaits elucidation.
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- 2018
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40. Smoking is Associated to DNA Methylation in Atherosclerotic Carotid Lesions
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Siemelink, Marten A., primary, van der Laan, Sander W., additional, Haitjema, Saskia, additional, van Koeverden, Ian D., additional, Schaap, Jacco, additional, Wesseling, Marian, additional, de Jager, Saskia C.A., additional, Mokry, Michal, additional, van Iterson, Maarten, additional, Dekkers, Koen F., additional, Luijk, René, additional, Foroughi Asl, Hassan, additional, Michoel, Tom, additional, Björkegren, Johan L.M., additional, Aavik, Einari, additional, Ylä-Herttuala, Seppo, additional, de Borst, Gert J., additional, Asselbergs, Folkert W., additional, el Azzouzi, Hamid, additional, den Ruijter, Hester M., additional, Heijmans, Bas T., additional, and Pasterkamp, Gerard, additional
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- 2018
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- View/download PDF
41. Smoking is Associated to DNA Methylation in Atherosclerotic Carotid Lesions
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Siemelink, MA, van der Laan, S.W., Haitjema, S, van Koeverden, ID, Schaap, J, Wesseling, M, de Jager, SCA, Mokry, M, Van Iterson, Maarten, Dekkers, Koen F, Luijk, René, Foroughi Asl, Hassan, Björkegren, Johan L M, Aavik, Einari, Ylä-Herttuala, Seppo, de Borst, GJ, Asselbergs, FW, el Azzouzi, H, den Ruijter, HM, Heijmans, Bastiaan T., Pasterkamp, G, Siemelink, MA, van der Laan, S.W., Haitjema, S, van Koeverden, ID, Schaap, J, Wesseling, M, de Jager, SCA, Mokry, M, Van Iterson, Maarten, Dekkers, Koen F, Luijk, René, Foroughi Asl, Hassan, Björkegren, Johan L M, Aavik, Einari, Ylä-Herttuala, Seppo, de Borst, GJ, Asselbergs, FW, el Azzouzi, H, den Ruijter, HM, Heijmans, Bastiaan T., and Pasterkamp, G
- Published
- 2018
42. Smoking is Associated to DNA Methylation in Atherosclerotic Carotid Lesions
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Experimentele Afd. Cardiologie 1, Circulatory Health, Divisie Biomedische Genetica, Onderzoek Vrouw Hart & Vaatziekten, Team Medisch, Cardiologie, MDL onderzoek 1, Child Health, Brain, Zorgeenheid Vaatchirurgie Medisch, CDL Staf Research, Experimentele Afd. Cardiologie 2, Cardiovasculaire Immunologie, Infection & Immunity, Onderzoek Cardiovasculair Reg. Med., Siemelink, MA, van der Laan, S.W., Haitjema, S, van Koeverden, ID, Schaap, J, Wesseling, M, de Jager, SCA, Mokry, M, Van Iterson, Maarten, Dekkers, Koen F, Luijk, René, Foroughi Asl, Hassan, Björkegren, Johan L M, Aavik, Einari, Ylä-Herttuala, Seppo, de Borst, GJ, Asselbergs, FW, el Azzouzi, H, den Ruijter, HM, Heijmans, Bastiaan T., Pasterkamp, G, Experimentele Afd. Cardiologie 1, Circulatory Health, Divisie Biomedische Genetica, Onderzoek Vrouw Hart & Vaatziekten, Team Medisch, Cardiologie, MDL onderzoek 1, Child Health, Brain, Zorgeenheid Vaatchirurgie Medisch, CDL Staf Research, Experimentele Afd. Cardiologie 2, Cardiovasculaire Immunologie, Infection & Immunity, Onderzoek Cardiovasculair Reg. Med., Siemelink, MA, van der Laan, S.W., Haitjema, S, van Koeverden, ID, Schaap, J, Wesseling, M, de Jager, SCA, Mokry, M, Van Iterson, Maarten, Dekkers, Koen F, Luijk, René, Foroughi Asl, Hassan, Björkegren, Johan L M, Aavik, Einari, Ylä-Herttuala, Seppo, de Borst, GJ, Asselbergs, FW, el Azzouzi, H, den Ruijter, HM, Heijmans, Bastiaan T., and Pasterkamp, G
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- 2018
43. Blood lipids influence DNA methylation in circulating cells
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Dekkers, Koen F, van Iterson, Maarten, Slieker, Roderick C, Moed, Matthijs H, Bonder, Marc Jan, van Galen, Michiel, Mei, Hailiang, Zhernakova, Daria V, van den Berg, Leonard H, Deelen, Joris, van Dongen, Jenny, van Heemst, Diana, Hofman, Albert, Hottenga, Jouke J, van der Kallen, Carla J H, Schalkwijk, Casper G, Stehouwer, Coen D A, Tigchelaar, Ettje F, Uitterlinden, André G, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, 't Hoen, Peter A C, Jansen, Rick, van Meurs, Joyce, Boomsma, Dorret I, van Duijn, Cornelia M, van Greevenbroek, Marleen M J, Veldink, Jan H, Wijmenga, Cisca, van Zwet, Erik W, Slagboom, P Eline, Jukema, J Wouter, Heijmans, Bastiaan T, BIOS Consortium, Dekkers, Koen F, van Iterson, Maarten, Slieker, Roderick C, Moed, Matthijs H, Bonder, Marc Jan, van Galen, Michiel, Mei, Hailiang, Zhernakova, Daria V, van den Berg, Leonard H, Deelen, Joris, van Dongen, Jenny, van Heemst, Diana, Hofman, Albert, Hottenga, Jouke J, van der Kallen, Carla J H, Schalkwijk, Casper G, Stehouwer, Coen D A, Tigchelaar, Ettje F, Uitterlinden, André G, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, 't Hoen, Peter A C, Jansen, Rick, van Meurs, Joyce, Boomsma, Dorret I, van Duijn, Cornelia M, van Greevenbroek, Marleen M J, Veldink, Jan H, Wijmenga, Cisca, van Zwet, Erik W, Slagboom, P Eline, Jukema, J Wouter, Heijmans, Bastiaan T, and BIOS Consortium
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- 2016
44. Blood lipids influence DNA methylation in circulating cells
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Projectafdeling ALS, Brain, Regenerative Medicine and Stem Cells, ZL Neuromusculaire Ziekten Medisch, Neurogenetica, Dekkers, Koen F, van Iterson, Maarten, Slieker, Roderick C, Moed, Matthijs H, Bonder, Marc Jan, van Galen, Michiel, Mei, Hailiang, Zhernakova, Daria V, van den Berg, Leonard H, Deelen, Joris, van Dongen, Jenny, van Heemst, Diana, Hofman, Albert, Hottenga, Jouke J, van der Kallen, Carla J H, Schalkwijk, Casper G, Stehouwer, Coen D A, Tigchelaar, Ettje F, Uitterlinden, André G, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, 't Hoen, Peter A C, Jansen, Rick, van Meurs, Joyce, Boomsma, Dorret I, van Duijn, Cornelia M, van Greevenbroek, Marleen M J, Veldink, Jan H, Wijmenga, Cisca, van Zwet, Erik W, Slagboom, P Eline, Jukema, J Wouter, Heijmans, Bastiaan T, BIOS Consortium, Projectafdeling ALS, Brain, Regenerative Medicine and Stem Cells, ZL Neuromusculaire Ziekten Medisch, Neurogenetica, Dekkers, Koen F, van Iterson, Maarten, Slieker, Roderick C, Moed, Matthijs H, Bonder, Marc Jan, van Galen, Michiel, Mei, Hailiang, Zhernakova, Daria V, van den Berg, Leonard H, Deelen, Joris, van Dongen, Jenny, van Heemst, Diana, Hofman, Albert, Hottenga, Jouke J, van der Kallen, Carla J H, Schalkwijk, Casper G, Stehouwer, Coen D A, Tigchelaar, Ettje F, Uitterlinden, André G, Willemsen, Gonneke, Zhernakova, Alexandra, Franke, Lude, 't Hoen, Peter A C, Jansen, Rick, van Meurs, Joyce, Boomsma, Dorret I, van Duijn, Cornelia M, van Greevenbroek, Marleen M J, Veldink, Jan H, Wijmenga, Cisca, van Zwet, Erik W, Slagboom, P Eline, Jukema, J Wouter, Heijmans, Bastiaan T, and BIOS Consortium
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- 2016
45. Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis.
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Mandaviya, Pooja R, Aïssi, Dylan, Dekkers, Koen F, Joehanes, Roby, Kasela, Silva, Truong, Vinh, Stolk, Lisette, Heemst, Diana van, Ikram, M Arfan, Lindemans, Jan, Slagboom, P Eline, Trégouët, David-Alexandre, Uitterlinden, André G, Wei, Chen, Wells, Phil, Gagnon, France, van Greevenbroek, Marleen MJ, Heijmans, Bastiaan T, Milani, Lili, and Morange, Pierre-Emmanuel
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- 2017
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46. Blood lipids influence DNA methylation in circulating cells.
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Dekkers, Koen F., van Iterson, Maarten, Slieker, Roderick C., Moed, Matthijs H., Bonder, Marc Jan, van Galen, Michiel, Hailiang Mei, Zhernakova, Daria V., van den Berg, Leonard H., Deelen, Joris, van Dongen, Jenny, van Heemst, Diana, Hofman, Albert, Hottenga, Jouke J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Stehouwer, Coen D. A., Tigchelaar, Ettje F., Uitterlinden, André G., and Willemsen, Gonneke
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- 2016
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47. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood
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Tobi, Elmar W., Slieker, Roderick C., Luijk, René, Dekkers, Koen F., Stein, Aryeh D., Xu, Kate M., Biobank-Based Integrative Omics Studies Consortium, Slagboom, P. Eline, Van Zwet, Erik W., Lumey, L. H., and Heijmans, Bastiaan T.
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2. Zero hunger ,DNA--Methylation ,FOS: Biological sciences ,Genetics ,Epigenetics ,Metabolism--Disorders ,Pregnant women--Health and hygiene - Abstract
Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis. DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing β cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-term metabolic health. The specific mechanism awaits elucidation.
48. Smoking is Associated to DNA Methylation in Atherosclerotic Carotid Lesions.
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Siemelink, Marten A., van der Laan, Sander W., Haitjema, Saskia, van Koeverden, Ian D., Schaap, Jacco, Wesseling, Marian, de Jager, Saskia C.A., Mokry, Michal, van Iterson, Maarten, Dekkers, Koen F., Luijk, René, Foroughi Asl, Hassan, Michoel, Tom, Björkegren, Johan L.M., Aavik, Einari, Ylä-Herttuala, Seppo, de Borst, Gert J., Asselbergs, Folkert W., el Azzouzi, Hamid, and den Ruijter, Hester M.
- Abstract
Supplemental Digital Content is available in the text. Background: Tobacco smoking is a major risk factor for atherosclerotic disease and has been associated with DNA methylation (DNAm) changes in blood cells. However, whether smoking influences DNAm in the diseased vascular wall is unknown but may prove crucial in understanding the pathophysiology of atherosclerosis. In this study, we associated current tobacco smoking to epigenome-wide DNAm in atherosclerotic plaques from patients undergoing carotid endarterectomy. Methods: DNAm at commonly methylated sites (cytosine-guanine nucleotide pairs separated by a phospho-group [CpGs]) was assessed in atherosclerotic plaque samples and peripheral blood samples from 485 carotid endarterectomy patients. We tested the association of current tobacco smoking with DNAm corrected for age and sex. To control for bias and inflation because of cellular heterogeneity, we applied a Bayesian method to estimate an empirical null distribution as implemented by the R package bacon. Replication of the smoking-associated methylated CpGs in atherosclerotic plaques was executed in the second sample of 190 carotid endarterectomy patients, and results were meta-analyzed using a fixed-effects model. Results: Tobacco smoking was significantly associated to differential DNAm in atherosclerotic lesions of 4 CpGs (false discovery rate <0.05) mapped to 2 different genes (AHRR , ITPK1) and 17 CpGs mapped to 8 genes and RNAs in blood. The strongest associations were found for CpGs mapped to the gene AHRR , a repressor of the aryl hydrocarbon receptor transcription factor involved in xenobiotic detoxification. One of these methylated CpGs were found to be regulated by local genetic variation. Conclusions: The risk factor tobacco smoking associates with DNAm at multiple loci in carotid atherosclerotic lesions. These observations support further investigation of the relationship between risk factors and epigenetic regulation in atherosclerotic disease. [ABSTRACT FROM AUTHOR]
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- 2018
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49. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
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Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, Carnero-Montoro E, Lawson DJ, Burrows K, Suderman M, Bretherick AD, Richardson TG, Klughammer J, Iotchkova V, Sharp G, Al Khleifat A, Shatunov A, Iacoangeli A, McArdle WL, Ho KM, Kumar A, Söderhäll C, Soriano-Tárraga C, Giralt-Steinhauer E, Kazmi N, Mason D, McRae AF, Corcoran DL, Sugden K, Kasela S, Cardona A, Day FR, Cugliari G, Viberti C, Guarrera S, Lerro M, Gupta R, Bollepalli S, Mandaviya P, Zeng Y, Clarke TK, Walker RM, Schmoll V, Czamara D, Ruiz-Arenas C, Rezwan FI, Marioni RE, Lin T, Awaloff Y, Germain M, Aïssi D, Zwamborn R, van Eijk K, Dekker A, van Dongen J, Hottenga JJ, Willemsen G, Xu CJ, Barturen G, Català-Moll F, Kerick M, Wang C, Melton P, Elliott HR, Shin J, Bernard M, Yet I, Smart M, Gorrie-Stone T, Shaw C, Al Chalabi A, Ring SM, Pershagen G, Melén E, Jiménez-Conde J, Roquer J, Lawlor DA, Wright J, Martin NG, Montgomery GW, Moffitt TE, Poulton R, Esko T, Milani L, Metspalu A, Perry JRB, Ong KK, Wareham NJ, Matullo G, Sacerdote C, Panico S, Caspi A, Arseneault L, Gagnon F, Ollikainen M, Kaprio J, Felix JF, Rivadeneira F, Tiemeier H, van IJzendoorn MH, Uitterlinden AG, Jaddoe VWV, Haley C, McIntosh AM, Evans KL, Murray A, Räikkönen K, Lahti J, Nohr EA, Sørensen TIA, Hansen T, Morgen CS, Binder EB, Lucae S, Gonzalez JR, Bustamante M, Sunyer J, Holloway JW, Karmaus W, Zhang H, Deary IJ, Wray NR, Starr JM, Beekman M, van Heemst D, Slagboom PE, Morange PE, Trégouët DA, Veldink JH, Davies GE, de Geus EJC, Boomsma DI, Vonk JM, Brunekreef B, Koppelman GH, Alarcón-Riquelme ME, Huang RC, Pennell CE, van Meurs J, Ikram MA, Hughes AD, Tillin T, Chaturvedi N, Pausova Z, Paus T, Spector TD, Kumari M, Schalkwyk LC, Visscher PM, Davey Smith G, Bock C, Gaunt TR, Bell JT, Heijmans BT, Mill J, and Relton CL
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- Chromosome Mapping, Epigenesis, Genetic genetics, Genome-Wide Association Study, Humans, Multifactorial Inheritance genetics, Polymorphism, Single Nucleotide genetics, Quantitative Trait, Heritable, Transcriptome genetics, DNA metabolism, DNA Methylation genetics, Gene Expression Regulation genetics, Genetic Predisposition to Disease genetics, Quantitative Trait Loci genetics
- Abstract
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2021
- Full Text
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