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
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 R. B.
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
van IJzendoorn, Marinus H.
Uitterlinden, André G.
Jaddoe, Vincent W. V.
Haley, Chris
McIntosh, Andrew M.
Evans, Kathryn L.
Murray, Alison
Räikkönen, Katri
Lahti, Jari
Nohr, Ellen A.
Sørensen, Thorkild I. A.
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 J. C.
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.
Davey Smith, George
Bock, Christoph
Gaunt, Tom R.
Bell, Jordana T.
Heijmans, Bastiaan T.
Mill, Jonathan
Relton, Caroline L.
Published Version
https://doi.org/10.1038/s41588-021-00923-xMetadata
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Min, Josine L., Gibran Hemani, Eilis Hannon, Koen F. Dekkers, Juan Castillo-Fernandez, René Luijk, Elena Carnero-Montoro et al. "Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation." Nat Genet 53, no. 9 (2021): 1311-1321. DOI: 10.1038/s41588-021-00923-xAbstract
Characterising 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 loci (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 mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both DNAm levels and complex diseases but only in a minority of cases these associations reflect direct causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than previously anticipated.Citable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376636
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