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  Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Min, J. L., Hemani, G., Hannon, E., Dekkers, K. F., Castillo-Fernandez, J., Luijk, R., Carnero-Montoro, E., Lawson, D. J., Burrows, K., Suderman, M., Bretherick, A. D., Richardson, T. G., Klughammer, J., Iotchkova, V., Sharp, G., Al Khleifat, A., Shatunov, A., Iacoangeli, A., McArdle, W. L., Ho, K. M., Kumar, A., Soderhall, C., Soriano-Tarraga, C., Giralt-Steinhauer, E., Kazmi, N., Mason, D., McRae, A. F., Corcoran, D. L., Sugden, K., Kasela, S., Cardona, A., Day, F. R., Cugliari, G., Viberti, C., Guarrera, S., Lerro, M., Gupta, R., Bollepalli, S., Mandaviya, P., Zeng, Y., Clarke, T.-K., Walker, R. M., Schmoll, V., Czamara, D., Ruiz-Arenas, C., Rezwan I, F., Marioni, R. E., Lin, T., Awaloff, Y., Germain, M., Aissi, D., Zwamborn, R., van Eijk, K., Dekker, A., van Dongen, J., Hottenga, J.-J., Willemsen, G., Xu, C.-J., Barturen, G., Catala-Moll, F., Kerick, M., Wang, C., Melton, P., Elliott, H. R., Shin, J., Bernard, M., Yet, I., Smarts, M., Gorrie-Stone, T., Shaw, C., Al Chalabi, A., Ring, S. M., Pershagen, G., Melen, E., Jimenez-Conde, J., Roquer, J., Lawlor, D. A., Wright, J., Martin, N. G., Montgomery, G. W., Moffitt, T. E., Poulton, R., Esko, T., Milani, L., Metspalu, A., Perry, J. R. B., Ong, K. K., Wareham, N. J., Matullo, G., Sacerdote, C., Panico, S., Caspi, A., Arseneault, L., Gagnon, F., Ollikainen, M., Kaprio, J., Felix, J. F., Rivadeneira, F., Tiemeier, H., van IJzendoorn, M. H., Uitterlinden, A. G., Jaddoe, V. W. V., Hale, C., McIntosh, A. M., Evans, K. L., Murray, A., Raikkonen, K., Lahti, J., Nohr, E. A., Sorensen, T. I. A., Hansen, T., Morgen, C. S., Binder, E. B., Lucae, S., Gonzalez, J. R., Bustamante, M., Sunyer, J., Holloway, J. W., Karmaus, W., Zhang, H., Deary, I. J., Wray, N. R., Starr, J. M., Beekman, M., VanHeemst, D., Slagboom, P. E., Morange, P.-E., Tregouet, D.-A., Veldink, J. H., Davies, G. E., de Geus, E. J. C., Boomsma I, D., Vonk, J. M., Brunekreef, B., Koppelman, G. H., Alarcon-Riquelme, M. E., Huang, R.-C., Pennell, C. E., van Meurs, J., Ikram, M. A., Hughes, A. D., Tillin, T., Chaturvedi, N., Pausova, Z., Paus, T., Spector, T. D., Kumari, M., Schalkwyk, L. C., Visscher, P. M., Smith, G. D., Bock, C., Gaunt, T. R., Bell, J. T., Heijmans, B. T., Mill, J., & Relton, C. L. (2021). Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation. NATURE GENETICS, 53(9), 1311-+. doi:10.1038/s41588-021-00923-x.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-0009-5366-7 版のパーマリンク: https://hdl.handle.net/21.11116/0000-0009-5367-6
資料種別: 学術論文

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作成者

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 作成者:
Min, Josine L., 著者
Hemani, Gibran, 著者
Hannon, Eilis, 著者
Dekkers, Koen F., 著者
Castillo-Fernandez, Juan, 著者
Luijk, Rene, 著者
Carnero-Montoro, Elena, 著者
Lawson, Daniel J., 著者
Burrows, Kimberley, 著者
Suderman, Matthew, 著者
Bretherick, Andrew D., 著者
Richardson, Tom G., 著者
Klughammer, Johanna, 著者
Iotchkova, Valentina, 著者
Sharp, Gemma, 著者
Al Khleifat, Ahmad, 著者
Shatunov, Aleksey, 著者
Iacoangeli, Alfredo, 著者
McArdle, Wendy L., 著者
Ho, Karen M., 著者
Kumar, Ashish, 著者Soderhall, Cilia, 著者Soriano-Tarraga, Carolina, 著者Giralt-Steinhauer, Eva, 著者Kazmi, Nabila, 著者Mason, Dan, 著者McRae, Allan F., 著者Corcoran, David L., 著者Sugden, Karen, 著者Kasela, Silva, 著者Cardona, Alexia, 著者Day, Felix R., 著者Cugliari, Giovanni, 著者Viberti, Clara, 著者Guarrera, Simonetta, 著者Lerro, Michael, 著者Gupta, Richa, 著者Bollepalli, Sailalitha, 著者Mandaviya, Pooja, 著者Zeng, Yanni, 著者Clarke, Toni-Kim, 著者Walker, Rosie M., 著者Schmoll, Vanessa1, 著者           Czamara, Darina1, 著者           Ruiz-Arenas, Carlos, 著者Rezwan I, Faisal, 著者Marioni, Riccardo E., 著者Lin, Tian, 著者Awaloff, Yvonne1, 著者           Germain, Marine, 著者Aissi, Dylan, 著者Zwamborn, Ramona, 著者van Eijk, Kristel, 著者Dekker, Annelot, 著者van Dongen, Jenny, 著者Hottenga, Jouke-Jan, 著者Willemsen, Gonneke, 著者Xu, Cheng-Jian, 著者Barturen, Guillermo, 著者Catala-Moll, Francesc, 著者Kerick, Martin, 著者Wang, Carol, 著者Melton, Phillip, 著者Elliott, Hannah R., 著者Shin, Jean, 著者Bernard, Manon, 著者Yet, Idil, 著者Smarts, Melissa, 著者Gorrie-Stone, Tyler, 著者Shaw, Chris, 著者Al Chalabi, Ammar, 著者Ring, Susan M., 著者Pershagen, Goran, 著者Melen, Erik, 著者Jimenez-Conde, Jordi, 著者Roquer, Jaume, 著者Lawlor, Deborah A., 著者Wright, John, 著者Martin, Nicholas G., 著者Montgomery, Grant W., 著者Moffitt, Terrie E., 著者Poulton, Richie, 著者Esko, Tonu, 著者Milani, Lili, 著者Metspalu, Andres, 著者Perry, John R. B., 著者Ong, Ken K., 著者Wareham, Nicholas J., 著者Matullo, Giuseppe, 著者Sacerdote, Carlotta, 著者Panico, Salvatore, 著者Caspi, Avshalom, 著者Arseneault, Louise, 著者Gagnon, France, 著者Ollikainen, Miina, 著者Kaprio, Jaakko, 著者Felix, Janine F., 著者Rivadeneira, Fernando, 著者Tiemeier, Henning, 著者van IJzendoorn, Marinus H., 著者Uitterlinden, Andre G., 著者Jaddoe, Vincent W. V., 著者Hale, Chris, 著者McIntosh, Andrew M., 著者Evans, Kathryn L., 著者Murray, Alison, 著者Raikkonen, Katri, 著者Lahti, Jari, 著者Nohr, Ellen A., 著者Sorensen, Thorkild I. A., 著者Hansen, Torben, 著者Morgen, Camilla S., 著者Binder, Elisabeth B.1, 著者           Lucae, Susanne2, 著者           Gonzalez, Juan Ramon, 著者Bustamante, Mariona, 著者Sunyer, Jordi, 著者Holloway, John W., 著者Karmaus, Wilfried, 著者Zhang, Hongmei, 著者Deary, Ian J., 著者Wray, Naomi R., 著者Starr, John M., 著者Beekman, Marian, 著者VanHeemst, Diana, 著者Slagboom, P. Eline, 著者Morange, Pierre-Emmanuel, 著者Tregouet, David-Alexandre, 著者Veldink, Jan H., 著者Davies, Gareth E., 著者de Geus, Eco J. C., 著者Boomsma I, Dorret, 著者Vonk, Judith M., 著者Brunekreef, Bert, 著者Koppelman, Gerard H., 著者Alarcon-Riquelme, Marta E., 著者Huang, Rae-Chi, 著者Pennell, Craig E., 著者van Meurs, Joyce, 著者Ikram, M. Arfan, 著者Hughes, Alun D., 著者Tillin, Therese, 著者Chaturvedi, Nish, 著者Pausova, Zdenka, 著者Paus, Tomas, 著者Spector, Timothy D., 著者Kumari, Meena, 著者Schalkwyk, Leonard C., 著者Visscher, Peter M., 著者Smith, George Davey, 著者Bock, Christoph, 著者Gaunt, Tom R., 著者Bell, Jordana T., 著者Heijmans, Bastiaan T., 著者Mill, Jonathan, 著者Relton, Caroline L., 著者 全て表示
所属:
1Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
2Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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 要旨: DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.
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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 日付: 2021
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: -
 識別子(DOI, ISBNなど): ISI: 000694666000011
DOI: 10.1038/s41588-021-00923-x
 学位: -

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出版物 1

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出版物名: NATURE GENETICS
種別: 学術雑誌
 著者・編者:
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出版社, 出版地: -
ページ: - 巻号: 53 (9) 通巻号: - 開始・終了ページ: 1311 - + 識別子(ISBN, ISSN, DOIなど): ISSN: 1061-4036