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, Rene; 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; Soderhall, Cilia; Soriano-Tarraga, 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 I, Faisal; Marioni, Riccardo E.; Lin, Tian; Awaloff, Yvonne; Germain, Marine; Aissi, Dylan; Zwamborn, Ramona; van Eijk, Kristel; Dekker, Annelot; van Dongen, Jenny; Hottenga, Jouke-Jan; Willemsen, Gonneke; Xu, Cheng-Jian; Barturen, Guillermo; Catala-Moll, Francesc; Kerick, Martin; Wang, Carol; Melton, Phillip; Elliott, Hannah R.; Shin, Jean; Bernard, Manon; Yet, Idil; Smarts, Melissa; Gorrie-Stone, Tyler; Shaw, Chris; Al Chalabi, Ammar; Ring, Susan M.; Pershagen, Goran; Melen, Erik; Jimenez-Conde, Jordi; Roquer, Jaume; Lawlor, Deborah A.; Wright, John; Martin, Nicholas G.; Montgomery, Grant W.; Moffitt, Terrie E.; Poulton, Richie; Esko, Tonu; 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; Tiemeier, Henning; van IJzendoorn, Marinus H.; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hale, Chris; McIntosh, Andrew M.; Evans, Kathryn L.; Murray, Alison; Raikkonen, Katri; Lahti, Jari; Nohr, Ellen A.; Sorensen, 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; VanHeemst, Diana; Slagboom, P. Eline; Morange, Pierre-Emmanuel; Tregouet, David-Alexandre; Veldink, Jan H.; Davies, Gareth E.; de Geus, Eco J. C.; Boomsma I, Dorret; Vonk, Judith M.; Brunekreef, Bert; Koppelman, Gerard H.; Alarcon-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.

doi:10.1038/s41588-021-00923-x

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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., et al. (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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Item Permalink: https://hdl.handle.net/21.11116/0000-0009-5366-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0009-5367-6

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Min, Josine L., Author
Hemani, Gibran, Author
Hannon, Eilis, Author
Dekkers, Koen F., Author
Castillo-Fernandez, Juan, Author
Luijk, Rene, Author
Carnero-Montoro, Elena, Author
Lawson, Daniel J., Author
Burrows, Kimberley, Author
Suderman, Matthew, Author
Bretherick, Andrew D., Author
Richardson, Tom G., Author
Klughammer, Johanna, Author
Iotchkova, Valentina, Author
Sharp, Gemma, Author
Al Khleifat, Ahmad, Author
Shatunov, Aleksey, Author
Iacoangeli, Alfredo, Author
McArdle, Wendy L., Author
Ho, Karen M., Author
Kumar, Ashish, AuthorSoderhall, Cilia, AuthorSoriano-Tarraga, Carolina, AuthorGiralt-Steinhauer, Eva, AuthorKazmi, Nabila, AuthorMason, Dan, AuthorMcRae, Allan F., AuthorCorcoran, David L., AuthorSugden, Karen, AuthorKasela, Silva, AuthorCardona, Alexia, AuthorDay, Felix R., AuthorCugliari, Giovanni, AuthorViberti, Clara, AuthorGuarrera, Simonetta, AuthorLerro, Michael, AuthorGupta, Richa, AuthorBollepalli, Sailalitha, AuthorMandaviya, Pooja, AuthorZeng, Yanni, AuthorClarke, Toni-Kim, AuthorWalker, Rosie M., AuthorSchmoll, Vanessa¹, Author Czamara, Darina¹, Author Ruiz-Arenas, Carlos, AuthorRezwan I, Faisal, AuthorMarioni, Riccardo E., AuthorLin, Tian, AuthorAwaloff, Yvonne¹, Author Germain, Marine, AuthorAissi, Dylan, AuthorZwamborn, Ramona, Authorvan Eijk, Kristel, AuthorDekker, Annelot, Authorvan Dongen, Jenny, AuthorHottenga, Jouke-Jan, AuthorWillemsen, Gonneke, AuthorXu, Cheng-Jian, AuthorBarturen, Guillermo, AuthorCatala-Moll, Francesc, AuthorKerick, Martin, AuthorWang, Carol, AuthorMelton, Phillip, AuthorElliott, Hannah R., AuthorShin, Jean, AuthorBernard, Manon, AuthorYet, Idil, AuthorSmarts, Melissa, AuthorGorrie-Stone, Tyler, AuthorShaw, Chris, AuthorAl Chalabi, Ammar, AuthorRing, Susan M., AuthorPershagen, Goran, AuthorMelen, Erik, AuthorJimenez-Conde, Jordi, AuthorRoquer, Jaume, AuthorLawlor, Deborah A., AuthorWright, John, AuthorMartin, Nicholas G., AuthorMontgomery, Grant W., AuthorMoffitt, Terrie E., AuthorPoulton, Richie, AuthorEsko, Tonu, AuthorMilani, Lili, AuthorMetspalu, Andres, AuthorPerry, John R. B., AuthorOng, Ken K., AuthorWareham, Nicholas J., AuthorMatullo, Giuseppe, AuthorSacerdote, Carlotta, AuthorPanico, Salvatore, AuthorCaspi, Avshalom, AuthorArseneault, Louise, AuthorGagnon, France, AuthorOllikainen, Miina, AuthorKaprio, Jaakko, AuthorFelix, Janine F., AuthorRivadeneira, Fernando, AuthorTiemeier, Henning, Authorvan IJzendoorn, Marinus H., AuthorUitterlinden, Andre G., AuthorJaddoe, Vincent W. V., AuthorHale, Chris, AuthorMcIntosh, Andrew M., AuthorEvans, Kathryn L., AuthorMurray, Alison, AuthorRaikkonen, Katri, AuthorLahti, Jari, AuthorNohr, Ellen A., AuthorSorensen, Thorkild I. A., AuthorHansen, Torben, AuthorMorgen, Camilla S., AuthorBinder, Elisabeth B.¹, Author Lucae, Susanne², Author Gonzalez, Juan Ramon, AuthorBustamante, Mariona, AuthorSunyer, Jordi, AuthorHolloway, John W., AuthorKarmaus, Wilfried, AuthorZhang, Hongmei, AuthorDeary, Ian J., AuthorWray, Naomi R., AuthorStarr, John M., AuthorBeekman, Marian, AuthorVanHeemst, Diana, AuthorSlagboom, P. Eline, AuthorMorange, Pierre-Emmanuel, AuthorTregouet, David-Alexandre, AuthorVeldink, Jan H., AuthorDavies, Gareth E., Authorde Geus, Eco J. C., AuthorBoomsma I, Dorret, AuthorVonk, Judith M., AuthorBrunekreef, Bert, AuthorKoppelman, Gerard H., AuthorAlarcon-Riquelme, Marta E., AuthorHuang, Rae-Chi, AuthorPennell, Craig E., Authorvan Meurs, Joyce, AuthorIkram, M. Arfan, AuthorHughes, Alun D., AuthorTillin, Therese, AuthorChaturvedi, Nish, AuthorPausova, Zdenka, AuthorPaus, Tomas, AuthorSpector, Timothy D., AuthorKumari, Meena, AuthorSchalkwyk, Leonard C., AuthorVisscher, Peter M., AuthorSmith, George Davey, AuthorBock, Christoph, AuthorGaunt, Tom R., AuthorBell, Jordana T., AuthorHeijmans, Bastiaan T., AuthorMill, Jonathan, AuthorRelton, Caroline L., Author more..

Affiliations:
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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Abstract: 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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Dates: Date issued: 2021

Publication Status: Issued

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Identifiers: ISI: 000694666000011
DOI: 10.1038/s41588-021-00923-x

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Title: NATURE GENETICS

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Pages: - Volume / Issue: 53 (9) Sequence Number: - Start / End Page: 1311 - + Identifier: ISSN: 1061-4036