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Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612069/ https://www.ncbi.nlm.nih.gov/pubmed/34493871 http://dx.doi.org/10.1038/s41588-021-00923-x |
| _version_ | 1783605330242961408 |
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| author | 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 Zeng, Yanni Clarke, Toni-Kim Walker, Rosie M Schmoll, Vanessa Czamara, Darina Ruiz-Arenas, Carlos Rezwan, Faisal I Marioni, Riccardo E Lin, Tian Awaloff, Yvonne Germain, Marine Aïssi, Dylan Zwamborn, Ramona van Eijk, Kristel Dekker, Annelot van Dongen, Jenny Hottenga, Jouke-Jan Willemsen, Gonneke Xu, Cheng-Jian Barturen, Guillermo Català-Moll, Francesc Kerick, Martin Wang, Carol Melton, Phillip Elliott, Hannah R Shin, Jean Bernard, Manon Yet, Idil Smart, Melissa Gorrie-Stone, Tyler Shaw, Chris Al Chalabi, Ammar Ring, Susan M Pershagen, Göran Melén, Erik Jiménez-Conde, Jordi Roquer, Jaume Lawlor, Deborah A Wright, John Martin, Nicholas G Montgomery, Grant W Moffitt, Terrie E Poulton, Richie Esko, Tõnu Milani, Lili Metspalu, Andres Perry, John RB Ong, Ken K Wareham, Nicholas J Matullo, Giuseppe Sacerdote, Carlotta Panico, Salvatore Caspi, Avshalom Arseneault, Louise Gagnon, France Ollikainen, Miina Kaprio, Jaakko Felix, Janine F Rivadeneira, Fernando Tiemeier, Henning van IJzendoorn, Marinus H Uitterlinden, André G Jaddoe, Vincent WV Haley, Chris McIntosh, Andrew M Evans, Kathryn L Murray, Alison Räikkönen, Katri Lahti, Jari Nohr, Ellen A Sørensen, Thorkild IA Hansen, Torben Morgen, Camilla S Binder, Elisabeth B Lucae, Susanne Gonzalez, Juan Ramon Bustamante, Mariona Sunyer, Jordi Holloway, John W Karmaus, Wilfried Zhang, Hongmei Deary, Ian J Wray, Naomi R Starr, John M Beekman, Marian van Heemst, Diana Slagboom, P Eline Morange, Pierre-Emmanuel Trégouët, David-Alexandre Veldink, Jan H Davies, Gareth E de Geus, Eco JC Boomsma, Dorret I Vonk, Judith M Brunekreef, Bert Koppelman, Gerard H Alarcón-Riquelme, Marta E Huang, Rae-Chi Pennell, Craig E van Meurs, Joyce Ikram, M Arfan Hughes, Alun D Tillin, Therese Chaturvedi, Nish Pausova, Zdenka Paus, Tomas Spector, Timothy D Kumari, Meena Schalkwyk, Leonard C Visscher, Peter M Smith, George Davey Bock, Christoph Gaunt, Tom R Bell, Jordana T Heijmans, Bastiaan T Mill, Jonathan Relton, Caroline L |
| author_facet | 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 Zeng, Yanni Clarke, Toni-Kim Walker, Rosie M Schmoll, Vanessa Czamara, Darina Ruiz-Arenas, Carlos Rezwan, Faisal I Marioni, Riccardo E Lin, Tian Awaloff, Yvonne Germain, Marine Aïssi, Dylan Zwamborn, Ramona van Eijk, Kristel Dekker, Annelot van Dongen, Jenny Hottenga, Jouke-Jan Willemsen, Gonneke Xu, Cheng-Jian Barturen, Guillermo Català-Moll, Francesc Kerick, Martin Wang, Carol Melton, Phillip Elliott, Hannah R Shin, Jean Bernard, Manon Yet, Idil Smart, Melissa Gorrie-Stone, Tyler Shaw, Chris Al Chalabi, Ammar Ring, Susan M Pershagen, Göran Melén, Erik Jiménez-Conde, Jordi Roquer, Jaume Lawlor, Deborah A Wright, John Martin, Nicholas G Montgomery, Grant W Moffitt, Terrie E Poulton, Richie Esko, Tõnu Milani, Lili Metspalu, Andres Perry, John RB Ong, Ken K Wareham, Nicholas J Matullo, Giuseppe Sacerdote, Carlotta Panico, Salvatore Caspi, Avshalom Arseneault, Louise Gagnon, France Ollikainen, Miina Kaprio, Jaakko Felix, Janine F Rivadeneira, Fernando Tiemeier, Henning van IJzendoorn, Marinus H Uitterlinden, André G Jaddoe, Vincent WV Haley, Chris McIntosh, Andrew M Evans, Kathryn L Murray, Alison Räikkönen, Katri Lahti, Jari Nohr, Ellen A Sørensen, Thorkild IA Hansen, Torben Morgen, Camilla S Binder, Elisabeth B Lucae, Susanne Gonzalez, Juan Ramon Bustamante, Mariona Sunyer, Jordi Holloway, John W Karmaus, Wilfried Zhang, Hongmei Deary, Ian J Wray, Naomi R Starr, John M Beekman, Marian van Heemst, Diana Slagboom, P Eline Morange, Pierre-Emmanuel Trégouët, David-Alexandre Veldink, Jan H Davies, Gareth E de Geus, Eco JC Boomsma, Dorret I Vonk, Judith M Brunekreef, Bert Koppelman, Gerard H Alarcón-Riquelme, Marta E Huang, Rae-Chi Pennell, Craig E van Meurs, Joyce Ikram, M Arfan Hughes, Alun D Tillin, Therese Chaturvedi, Nish Pausova, Zdenka Paus, Tomas Spector, Timothy D Kumari, Meena Schalkwyk, Leonard C Visscher, Peter M Smith, George Davey Bock, Christoph Gaunt, Tom R Bell, Jordana T Heijmans, Bastiaan T Mill, Jonathan Relton, Caroline L |
| author_sort | Min, Josine L |
| collection | PubMed |
| description | Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-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 construct 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. |
| format | Online Article Text |
| id | pubmed-7612069 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-76120692022-03-06 Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation 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 Zeng, Yanni Clarke, Toni-Kim Walker, Rosie M Schmoll, Vanessa Czamara, Darina Ruiz-Arenas, Carlos Rezwan, Faisal I Marioni, Riccardo E Lin, Tian Awaloff, Yvonne Germain, Marine Aïssi, Dylan Zwamborn, Ramona van Eijk, Kristel Dekker, Annelot van Dongen, Jenny Hottenga, Jouke-Jan Willemsen, Gonneke Xu, Cheng-Jian Barturen, Guillermo Català-Moll, Francesc Kerick, Martin Wang, Carol Melton, Phillip Elliott, Hannah R Shin, Jean Bernard, Manon Yet, Idil Smart, Melissa Gorrie-Stone, Tyler Shaw, Chris Al Chalabi, Ammar Ring, Susan M Pershagen, Göran Melén, Erik Jiménez-Conde, Jordi Roquer, Jaume Lawlor, Deborah A Wright, John Martin, Nicholas G Montgomery, Grant W Moffitt, Terrie E Poulton, Richie Esko, Tõnu Milani, Lili Metspalu, Andres Perry, John RB Ong, Ken K Wareham, Nicholas J Matullo, Giuseppe Sacerdote, Carlotta Panico, Salvatore Caspi, Avshalom Arseneault, Louise Gagnon, France Ollikainen, Miina Kaprio, Jaakko Felix, Janine F Rivadeneira, Fernando Tiemeier, Henning van IJzendoorn, Marinus H Uitterlinden, André G Jaddoe, Vincent WV Haley, Chris McIntosh, Andrew M Evans, Kathryn L Murray, Alison Räikkönen, Katri Lahti, Jari Nohr, Ellen A Sørensen, Thorkild IA Hansen, Torben Morgen, Camilla S Binder, Elisabeth B Lucae, Susanne Gonzalez, Juan Ramon Bustamante, Mariona Sunyer, Jordi Holloway, John W Karmaus, Wilfried Zhang, Hongmei Deary, Ian J Wray, Naomi R Starr, John M Beekman, Marian van Heemst, Diana Slagboom, P Eline Morange, Pierre-Emmanuel Trégouët, David-Alexandre Veldink, Jan H Davies, Gareth E de Geus, Eco JC Boomsma, Dorret I Vonk, Judith M Brunekreef, Bert Koppelman, Gerard H Alarcón-Riquelme, Marta E Huang, Rae-Chi Pennell, Craig E van Meurs, Joyce Ikram, M Arfan Hughes, Alun D Tillin, Therese Chaturvedi, Nish Pausova, Zdenka Paus, Tomas Spector, Timothy D Kumari, Meena Schalkwyk, Leonard C Visscher, Peter M Smith, George Davey Bock, Christoph Gaunt, Tom R Bell, Jordana T Heijmans, Bastiaan T Mill, Jonathan Relton, Caroline L Nat Genet Article Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-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 construct 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. 2021-09-01 2021-09-06 /pmc/articles/PMC7612069/ /pubmed/34493871 http://dx.doi.org/10.1038/s41588-021-00923-x Text en https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms |
| spellingShingle | Article 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 Zeng, Yanni Clarke, Toni-Kim Walker, Rosie M Schmoll, Vanessa Czamara, Darina Ruiz-Arenas, Carlos Rezwan, Faisal I Marioni, Riccardo E Lin, Tian Awaloff, Yvonne Germain, Marine Aïssi, Dylan Zwamborn, Ramona van Eijk, Kristel Dekker, Annelot van Dongen, Jenny Hottenga, Jouke-Jan Willemsen, Gonneke Xu, Cheng-Jian Barturen, Guillermo Català-Moll, Francesc Kerick, Martin Wang, Carol Melton, Phillip Elliott, Hannah R Shin, Jean Bernard, Manon Yet, Idil Smart, Melissa Gorrie-Stone, Tyler Shaw, Chris Al Chalabi, Ammar Ring, Susan M Pershagen, Göran Melén, Erik Jiménez-Conde, Jordi Roquer, Jaume Lawlor, Deborah A Wright, John Martin, Nicholas G Montgomery, Grant W Moffitt, Terrie E Poulton, Richie Esko, Tõnu Milani, Lili Metspalu, Andres Perry, John RB Ong, Ken K Wareham, Nicholas J Matullo, Giuseppe Sacerdote, Carlotta Panico, Salvatore Caspi, Avshalom Arseneault, Louise Gagnon, France Ollikainen, Miina Kaprio, Jaakko Felix, Janine F Rivadeneira, Fernando Tiemeier, Henning van IJzendoorn, Marinus H Uitterlinden, André G Jaddoe, Vincent WV Haley, Chris McIntosh, Andrew M Evans, Kathryn L Murray, Alison Räikkönen, Katri Lahti, Jari Nohr, Ellen A Sørensen, Thorkild IA Hansen, Torben Morgen, Camilla S Binder, Elisabeth B Lucae, Susanne Gonzalez, Juan Ramon Bustamante, Mariona Sunyer, Jordi Holloway, John W Karmaus, Wilfried Zhang, Hongmei Deary, Ian J Wray, Naomi R Starr, John M Beekman, Marian van Heemst, Diana Slagboom, P Eline Morange, Pierre-Emmanuel Trégouët, David-Alexandre Veldink, Jan H Davies, Gareth E de Geus, Eco JC Boomsma, Dorret I Vonk, Judith M Brunekreef, Bert Koppelman, Gerard H Alarcón-Riquelme, Marta E Huang, Rae-Chi Pennell, Craig E van Meurs, Joyce Ikram, M Arfan Hughes, Alun D Tillin, Therese Chaturvedi, Nish Pausova, Zdenka Paus, Tomas Spector, Timothy D Kumari, Meena Schalkwyk, Leonard C Visscher, Peter M Smith, George Davey Bock, Christoph Gaunt, Tom R Bell, Jordana T Heijmans, Bastiaan T Mill, Jonathan Relton, Caroline L Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation |
| title | Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation |
| title_full | Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation |
| title_fullStr | Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation |
| title_full_unstemmed | Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation |
| title_short | Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation |
| title_sort | genomic and phenotypic insights from an atlas of genetic effects on dna methylation |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612069/ https://www.ncbi.nlm.nih.gov/pubmed/34493871 http://dx.doi.org/10.1038/s41588-021-00923-x |
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