Min, Josine L.Hemani, GibranHannon, EilisDekkers, Koen F.Castillo-Fernandez, JuanLuijk, RenéCarnero-Montoro, ElenaLawson, Daniel J.Burrows, KimberleySuderman, MatthewBretherick, Andrew D.Richardson, Tom G.Klughammer, JohannaIotchkova, ValentinaSharp, GemmaAl Khleifat, AhmadShatunov, AlekseyIacoangeli, AlfredoMcArdle, Wendy L.Ho, Karen M.Kumar, AshishSöderhäll, CillaSoriano-Tárraga, CarolinaGiralt-Steinhauer, EvaKazmi, NabilaMason, DanMcRae, Allan F.Corcoran, David L.Sugden, KarenKasela, SilvaCardona, AlexiaDay, Felix R.Cugliari, GiovanniViberti, ClaraGuarrera, SimonettaLerro, MichaelGupta, RichaBollepalli, SailalithaMandaviya, PoojaZeng, YanniClarke, Toni-KimWalker, Rosie M.Schmoll, VanessaCzamara, DarinaRuiz-Arenas, CarlosRezwan, Faisal I.Marioni, Riccardo E.Lin, TianAwaloff, YvonneGermain, MarineAïssi, DylanZwamborn, Ramonavan Eijk, KristelDekker, Annelotvan Dongen, JennyHottenga, Jouke-JanWillemsen, GonnekeXu, Cheng-JianBarturen, GuillermoCatalà-Moll, FrancescKerick, MartinWang, CarolMelton, PhillipElliott, Hannah R.Shin, JeanBernard, ManonYet, IdilSmart, MelissaGorrie-Stone, TylerShaw, ChrisAl Chalabi, AmmarRing, Susan M.Pershagen, GöranMelén, ErikJiménez-Conde, JordiRoquer, JaumeLawlor, Deborah A.Wright, JohnMartin, Nicholas G.Montgomery, Grant W.Moffitt, Terrie E.Poulton, RichieEsko, TõnuMilani, LiliMetspalu, AndresPerry, John R. B.Ong, Ken K.Wareham, Nicholas J.Matullo, GiuseppeSacerdote, CarlottaPanico, SalvatoreCaspi, AvshalomArseneault, LouiseGagnon, FranceOllikainen, MiinaKaprio, JaakkoFelix, Janine F.Rivadeneira, FernandoTiemeier, Henningvan IJzendoorn, Marinus H.Uitterlinden, André G.Jaddoe, Vincent W. V.Haley, ChrisMcIntosh, Andrew M.Evans, Kathryn L.Murray, AlisonRäikkönen, KatriLahti, JariNohr, Ellen A.Sørensen, Thorkild I. A.Hansen, TorbenMorgen, Camilla S.Binder, Elisabeth B.Lucae, SusanneGonzalez, Juan RamonBustamante, MarionaSunyer, JordiHolloway, John W.Karmaus, WilfriedZhang, HongmeiDeary, Ian J.Wray, Naomi R.Starr, John M.Beekman, Marianvan Heemst, DianaSlagboom, P. ElineMorange, Pierre-EmmanuelTrégouët, David-AlexandreVeldink, Jan H.Davies, Gareth E.de Geus, Eco J. C.Boomsma, Dorret I.Vonk, Judith M.Brunekreef, BertKoppelman, Gerard H.Alarcón-Riquelme, Marta E.Huang, Rae-ChiPennell, Craig E.van Meurs, JoyceIkram, M. ArfanHughes, Alun D.Tillin, ThereseChaturvedi, NishPausova, ZdenkaPaus, TomasSpector, Timothy D.Kumari, MeenaSchalkwyk, Leonard C.Visscher, Peter M.Davey Smith, GeorgeBock, ChristophGaunt, Tom R.Bell, Jordana T.Heijmans, Bastiaan T.Mill, JonathanRelton, Caroline L.2023-07-272021-09Min, 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-x1061-40361546-1718https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376636NoneCharacterising 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.en-USGeneticsJournal Article2023-07-2710.1038/s41588-021-00923-x