TY - JOUR
T1 - Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
AU - BIOS Consortium
AU - Min, Josine L.
AU - Hemani, Gibran
AU - Hannon, Eilis
AU - Dekkers, Koen F.
AU - Castillo-Fernandez, Juan
AU - Luijk, René
AU - Carnero-Montoro, Elena
AU - Lawson, Daniel J.
AU - Burrows, Kimberley
AU - Suderman, Matthew
AU - Bretherick, Andrew D.
AU - Richardson, Tom G.
AU - Klughammer, Johanna
AU - Iotchkova, Valentina
AU - Sharp, Gemma
AU - Al Khleifat, Ahmad
AU - Shatunov, Aleksey
AU - Iacoangeli, Alfredo
AU - McArdle, Wendy L.
AU - Ho, Karen M.
AU - Kumar, Ashish
AU - Söderhäll, Cilla
AU - Soriano-Tárraga, Carolina
AU - Giralt-Steinhauer, Eva
AU - Kazmi, Nabila
AU - Mason, Dan
AU - McRae, Allan F.
AU - Corcoran, David L.
AU - Sugden, Karen
AU - Kasela, Silva
AU - Cardona, Alexia
AU - Day, Felix R.
AU - Cugliari, Giovanni
AU - Viberti, Clara
AU - Guarrera, Simonetta
AU - Lerro, Michael
AU - Gupta, Richa
AU - Bollepalli, Sailalitha
AU - Mandaviya, Pooja
AU - Zeng, Yanni
AU - Clarke, Toni Kim
AU - Walker, Rosie M.
AU - Schmoll, Vanessa
AU - Czamara, Darina
AU - Ruiz-Arenas, Carlos
AU - Rezwan, Faisal I.
AU - Marioni, Riccardo E.
AU - Lin, Tian
AU - Awaloff, Yvonne
AU - Germain, Marine
AU - Aïssi, Dylan
AU - Zwamborn, Ramona
AU - van Eijk, Kristel
AU - Dekker, Annelot
AU - van Dongen, Jenny
AU - Hottenga, Jouke Jan
AU - Willemsen, Gonneke
AU - Xu, Cheng Jian
AU - Barturen, Guillermo
AU - Català-Moll, Francesc
AU - Kerick, Martin
AU - Wang, Carol
AU - Melton, Phillip
AU - Elliott, Hannah R.
AU - Shin, Jean
AU - Bernard, Manon
AU - Yet, Idil
AU - Smart, Melissa
AU - Gorrie-Stone, Tyler
AU - Shaw, Chris
AU - Al Chalabi, Ammar
AU - Ring, Susan M.
AU - Pershagen, Göran
AU - Melén, Erik
AU - Jiménez-Conde, Jordi
AU - Roquer, Jaume
AU - Lawlor, Deborah A.
AU - Wright, John
AU - Martin, Nicholas G.
AU - Montgomery, Grant W.
AU - Moffitt, Terrie E.
AU - Poulton, Richie
AU - Esko, Tõnu
AU - Milani, Lili
AU - Metspalu, Andres
AU - Perry, John R.B.
AU - Ong, Ken K.
AU - Wareham, Nicholas J.
AU - Matullo, Giuseppe
AU - Sacerdote, Carlotta
AU - Panico, Salvatore
AU - Caspi, Avshalom
AU - Arseneault, Louise
AU - Gagnon, France
AU - Ollikainen, Miina
AU - Kaprio, Jaakko
AU - Felix, Janine F.
AU - Rivadeneira, Fernando
AU - Tiemeier, Henning
AU - van IJzendoorn, Marinus H.
AU - Uitterlinden, André G.
AU - Jaddoe, Vincent W.V.
AU - Haley, Chris
AU - McIntosh, Andrew M.
AU - Evans, Kathryn L.
AU - Murray, Alison
AU - Räikkönen, Katri
AU - Lahti, Jari
AU - Nohr, Ellen A.
AU - Sørensen, Thorkild I.A.
AU - Hansen, Torben
AU - Morgen, Camilla S.
AU - Binder, Elisabeth B.
AU - Lucae, Susanne
AU - Gonzalez, Juan Ramon
AU - Bustamante, Mariona
AU - Sunyer, Jordi
AU - Holloway, John W.
AU - Karmaus, Wilfried
AU - Zhang, Hongmei
AU - Deary, Ian J.
AU - Wray, Naomi R.
AU - Starr, John M.
AU - Beekman, Marian
AU - van Heemst, Diana
AU - Slagboom, P. Eline
AU - Morange, Pierre Emmanuel
AU - Trégouët, David Alexandre
AU - Veldink, Jan H.
AU - Davies, Gareth E.
AU - de Geus, Eco J.C.
AU - Boomsma, Dorret I.
AU - Vonk, Judith M.
AU - Brunekreef, Bert
AU - Koppelman, Gerard H.
AU - Alarcón-Riquelme, Marta E.
AU - Huang, Rae Chi
AU - Pennell, Craig E.
AU - van Meurs, Joyce
AU - Ikram, M. Arfan
AU - Hughes, Alun D.
AU - Tillin, Therese
AU - Chaturvedi, Nish
AU - Pausova, Zdenka
AU - Paus, Tomas
AU - Spector, Timothy D.
AU - Kumari, Meena
AU - Schalkwyk, Leonard C.
AU - Visscher, Peter M.
AU - Davey Smith, George
AU - Bock, Christoph
AU - Gaunt, Tom R.
AU - Bell, Jordana T.
AU - Heijmans, Bastiaan T.
AU - Mill, Jonathan
AU - Relton, Caroline L.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103124472&partnerID=8YFLogxK
U2 - 10.1038/s41588-021-00923-x
DO - 10.1038/s41588-021-00923-x
M3 - Article
C2 - 34493871
AN - SCOPUS:85103124472
SN - 1061-4036
VL - 53
SP - 1311
EP - 1321
JO - Nature Genetics
JF - Nature Genetics
IS - 9
ER -