University of Oulu

Czamara, D., Eraslan, G., Page, C.M. et al. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nat Commun 10, 2548 (2019). https://doi.org/10.1038/s41467-019-10461-0

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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Author: Czamara, Darina1; Eraslan, Goekcen2,3; Page, Christian M.4,5;
Lahti, Jari6,7; Lahti-Pulkkinen, Marius6,8; Hamalainen, Esa9,10; Kajantie, Eero11,12,13,14,15; Laivuori, Hannele16,17,18,19,20; Villa, Pia M.16,17; Reynolds, Rebecca M.8; Nystad, Wenche21; Haberg, Siri E.5; London, Stephanie J.22; O'Donnell, Kieran J.23,24; Garg, Elika23; Meaney, Michael J.23,24,25; Entringer, Sonja26,27,28,29,30; Wadhwa, Pathik D.30,31; Buss, Claudia26,27,28,29,30; Jones, Meaghan J.32,33; Lin, David T. S.32,33; MacIsaac, Julie L.32,33; Kobor, Michael S.32,33; Koen, Nastassja34,35; Zar, Heather J.36,37; Koenen, Karestan C.38; Dalvie, Shareefa34; Stein, Dan J.34,35; Kondofersky, Ivan2,39; Mueller, Nikola S.2; Theis, Fabian J.2,39; Raikkonen, Katri6; Binder, Elisabeth B.1,40; Wray, Naomi R.41,42; Ripke, Stephan43,44,45; Mattheisen, Manuel46,47,48,49; Trzaskowski, Maciej41; Byrne, Enda M.41; Abdellaoui, Abdel50,51; Adams, Mark J.52; Agerbo, Esben49,53,54; Air, Tracy M.55; Andlauer, Till F. M.1,56; Bacanu, Silviu-Alin57; Baekvad-Hansen, Marie49,58; Beekman, Aartjan T. F.59,60; Bigdeli, Tim B.57,61; Blackwood, Douglas H. R.52; Bryois, Julien62; Buttenschon, Henriette N.48,49,63; Bybjerg-Grauholm, Jonas49,58; Cai, Na64,65; Castelao, Enrique66; Christensen, Jane Hvarregaard47,48,49; Clarke, Toni-Kim52; Coleman, Jonathan R., I67; Colodro-Conde, Lucia68; Couvy-Duchesne, Baptiste69,70; Craddock, Nick71; Crawford, Gregory E.72,73; Davies, Gail74; Deary, Ian J.74; Degenhardt, Franziska75,76; Derks, Eske M.68; Direk, Nese77,78; Dolan, Conor, V50,51; Dunn, Erin C.79,80,81; Eley, Thalia C.67; Escott-Price, Valentina82; Kiadeh, Farnush Farhadi Hassan83; Finucane, Hilary K.69,84; Forstner, Andreas J.75,76,85,86; Frank, Josef87; Gaspar, Helena A.67; Gill, Michael88; Goes, Fernando S.89; Gordon, Scott D.90; Grove, Jakob47,48,49,91; Hall, Lynsey S.52,92; Hansen, Christine Soholm49,58; Hansen, Thomas F.93,94,95; Herms, Stefan75,76,86; Hickie, Ian B.96; Hoffmann, Per57,75,76; Homuth, Georg97,98; Horn, Carsten99; Hottenga, Jouke-Jan50,51; Hougaard, David M.49,58; Ising, Marcus100; Jansen, Rick59,60; Jorgenson, Eric101; Knowles, James A.102; Kohane, Isaac S.103,104,105; Kraft, Julia44; Kretzschmar, Warren W.106; Krogh, Jesper107; Kutalik, Zoltan108,109; Li, Yihan106; Lind, Penelope A.68; MacIntyre, Donald J.110,111; MacKinnon, Dean F.89; Maier, Robert M.42; Maier, Wolfgang112; Marchini, Jonathan113; Mbarek, Hamdi50,51; McGrath, Patrick114; McGuffin, Peter67; Medland, Sarah E.68; Mehta, Divya42,115; Middeldorp, Christel M.50,51,116,117; Mihailov, Evelin118; Milaneschi, Yuri59,60; Milani, Lili118; Mondimore, Francis M.89; Montgomery, Grant W.42; Mostafavi, Sara119,120; Mullins, Niamh67; Nauck, Matthias121,122; Ng, Bernard120; Nivard, Michel G.50,51; Nyholt, Dale R.123; O'Reilly, Paul F.67; Oskarsson, Hogni124; Owen, Michael J.125; Painter, Jodie N.68; Pedersen, Carsten Bocker49,53,54; Pedersen, Marianne Girtz49,53,54; Peterson, Roseann E.57,126; Pettersson, Erik62; Peyrot, Wouter J.59,60; Pistis, Giorgio66; Posthuma, Danielle127,128; Quiroz, Jorge A.129; Qvist, Per47,48,49; Rice, John P.130; Riley, Brien P.57; Rivera, Margarita67,131; Mirza, Saira Saeed77; Schoevers, Robert132; Schulte, Eva C.133,134; Shen, Ling101; Shi, Jianxin135; Shyn, Stanley, I136; Sigurdsson, Engilbert137; Sinnamon, Grant C. B.138; Smit, Johannes H.59,60; Smith, Daniel J.139; Stefansson, Hreinn140; Steinberg, Stacy140; Streit, Fabian87; Strohmaier, Jana87; Tansey, Katherine E.141; Teismann, Henning142; Teumer, Alexander143; Thompson, Wesley49,94,144,145; Thomson, Pippa A.144; Thorgeirsson, Thorgeir E.140; Traylor, Matthew146; Treutlein, Jens87; Trubetskoy, Vassily44; Uitterlinden, Andre G.147; Umbricht, Daniel148; Van der Auwera, Sandra149; van Hemert, Albert M.150; Viktorin, Alexander62; Visscher, Peter M.41,42; Wang, Yunpeng49,94,145; Webb, Bradley T.126; Weinsheimer, Shantel Marie49,94; Wellmann, Juergen142; Willemsen, Gonneke50,51; Witt, Stephanie H.87; Wu, Yang41; Xi, Hualin S.151; Yang, Jian41,42; Zhang, Futao41; Arolt, Volker152; Baune, Bernhard T.55; Berger, Klaus142; Boomsma, Dorret, I50,51; Cichon, Sven75,86,153,154; Dannlowski, Udo152; de Geus, E. J. C.11,12,155; DePaulo, J. Raymond89; Domenici, Enrico156; Domschke, Katharina157; Esko, Tonu45,118; Grabe, Hans J.149; Hamilton, Steven P.158; Hayward, Caroline159; Heath, Andrew C.130; Kendler, Kenneth S.57; Kloiber, Stefan100,160,161; Lewis, Glyn162; Li, Qingqin S.163; Lucae, Susanne100; Madden, Pamela A. F.130; Magnusson, Patrik K.62; Martin, Nicholas G.90; McIntosh, Andrew M.52,74; Metspalu, Andres118,164; Mors, Ole49,165; Mortensen, Preben Bo48,49,53,54; Mueller-Myhsok, Bertram1,56,166; Nordentoft, Merete49,167; Noethen, Markus M.75,76; O'Donovan, Michael C.125; Paciga, Sara A.168; Pedersen, Nancy L.62; Penninx, Brenda W. J. H.59,60; Perlis, Roy H.79,169; Porteous, David J.170; Potash, James B.171; Preisig, Martin66; Rietschel, Marcella87; Schaefer, Catherine101; Schulze, Thomas G.87,134,172,173,174; Smoller, Jordan W.79,80,81; Stefansson, Kari165,175; Tiemeier, Henning77,176,177; Uher, Rudolf178; Voelzke, Henry143; Weissman, Myrna M.114,179; Werge, Thomas49,94,180; Lewis, Cathryn M.67,181; Levinson, Douglas F.182; Breen, Gerome67,183; Borglum, Anders D.47,48,49; Sullivan, Patrick F.62,184,185
Organizations: 1Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany.
2German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Computat Biol, D-85764 Neuherberg, Germany.
3Tech Univ Munich, Sch Life Sci, Weihenstephan, D-85354 Freising Weihenstephan, Germany.
4Oslo Univ Hosp, Res Support Unit, 0Slo Ctr Biostat & Epidemiol, N-0372 Oslo, Norway.
5Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, N-0213 Oslo, Norway.
6Univ Helsinki, Fac Med, Dept Psychol & Logoped, FIN-00014 Helsinki, Finland.
7Univ Helsinki, Helsinki Coll Adv Studies, Helsinki 00101, Finland.
8Univ Edinburgh, Queens Med Res Inst, British Heart Fdn Ctr Cardiovasc Sci, Edinburgh EH16 4TJ, Midlothian, Scotland.
9Univ Helsinki, HUSLAB, Helsinki 00290, Finland.
10Univ Helsinki, Dept Clin Chem, Helsinki 00290, Finland.
11Oulu Univ Hosp, Oulu 90014, Finland.
12Univ Oulu, PEDEGO Res Unit, MRC Oulu, Oulu 90014, Finland.
13Univ Helsinki, Hosp Children & Adolescents, Helsinki 00029, Finland.
14Helsinki Univ Hosp, Helsinki 00029, Finland.
15Natl Inst Hlth & Welf, Helsinki 00271, Finland.
16Univ Helsinki, Med & Clin Genet & Obstet & Gynaecol, Helsinki 00014, Finland.
17Helsinki Univ Cent Hosp, Helsinki 00014, Finland.
18Univ Helsinki, Helsinki Inst Life Sci, Lnstitute Mol Med Finland, FIN-00014 Helsinki, Finland.
19Univ Tampere, Fac Med & Life Sci, Tampere 33100, Finland.
20Tampere Univ Hosp, Dept Obstet & Gynecol, Tampere 33100, Finland.
21Norwegian Inst Publ Hlth, Dept Chron Dis & Ageing, N-0213 Oslo, Norway.
22NIEHS, Epidemiol Branch, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, MD 20814 USA.
23McGill Univ, Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ H3A 2B4, Canada.
24McGill Univ, Sackler Program Epigenet & Psychobiol, Montreal, PQ H3A 0G4, Canada.
25Singapore Inst Clin Sci, Singapore 117609, Singapore.
26Charite Univ Med Berlin, D-10117 Berlin, Germany.
27Free Univ Berlin, D-10117 Berlin, Germany.
28Humboldt Univ, D-10117 Berlin, Germany.
29Berlin Inst Hlth, Inst Med Psychol, D-10117 Berlin, Germany.
30Univ Calif Irvine, Dev Hlth & Dis Res Program, Orange, CA 92697 USA.
31Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav Obstet & Gynecol & Ep, Irvine, CA 92697 USA.
32Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada.
33BC Childrens Hosp Res Inst, Vancouver, BC V5Z 4H4, Canada.
34Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa.
35SAMRC, Unit Risk & Resilience Mental Disorders, ZA-7505 Cape Town, South Africa.
36Univ Cape Town, Dept Paediat & Child Hlth, ZA-7505 Cape Town, South Africa.
37Univ Cape Town, SAMRC Unit Child & Adolescent Hlth, ZA-7505 Cape Town, South Africa.
38Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
39Tech Univ Munich, Dept Math, D-85748 Munich, Germany.
40Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA.
41Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
42Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
43Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
44Univ Med Berlin, Dept Psychiat & Psychotherapy, Campus Charite Mitte, D-14129 Berlin, Germany.
45Broad Inst, Med & Populat Genet, Cambridge, MA 02142 USA.
46Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, SE-17177 Stockholm, Sweden.
47Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark.
48Aarhus Univ, Ctr Integrat Sequencing, iSEQ, DK-8000 Aarhus, Denmark.
49Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, DK-8000 Aarhus, Denmark.
50Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
51Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands.
52Univ Edinburgh, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland.
53Aarhus Univ, Ctr Integrated Register Based Res, DK-8210 Aarhus, Denmark.
54Aarhus Univ, Natl Ctr Register Based Res, DK-8210 Aarhus, Denmark.
55Univ Adelaide, Discipline Psychiat, Adelaide, SA 5000, Australia.
56Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany.
57Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 22903 USA.
58Statens Serum Inst, Dept Congenital Disorders, Ctr Neonatal Screening, DK-2300 Copenhagen, Denmark.
59Vrije Univ Med Ctr, Dept Psychiat, NL-1081 NL Amsterdam, Netherlands.
60GGZ InGeest, NL-1081 NL Amsterdam, Netherlands.
61Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA.
62Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
63Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, DK-8240 Aarhus, Denmark.
64Wellcome Trust Sanger Inst, Human Genet, Cambridge CB10 1SA, England.
65European Bioinformat Inst EMBL EBI, Stat Genom & Syst Genet, Cambridge CB10 1SD, England.
66Univ Hosp Lausanne, Dept Psychiat, CH-1004 Prilly, Vaud, Switzerland.
67Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
68QIMR Berghofer Med Res Inst, Genet & Computat Biol, Herston, Qld 4006, Australia.
69Univ Queensland, Ctr Adv Imaging, St Lucia, Qld 4072, Australia.
70Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
71Cardiff Univ, Psychol Med, Cardiff CF14 4XN, S Glam, Wales.
72Duke Univ, Ctr Genom & Computat Biol, Durham, NC 27705 USA.
73Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27708 USA.
74Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
75Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
76Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
77Erasmus MC, Epidemiol, NL-3015 Rotterdam, Zuid Holland, Netherlands.
78Dokuz Eylul Univ, Sch Med, Psychiat, TR-35220 Izmir, Turkey.
79Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
80Massachusetts Gen Hosp, PNGU, Boston, MA 02114 USA.
81Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
82Cardiff Univ, Neurosci & Mental Hlth, Cardiff CF24 4HQ, S Glam, Wales.
83Univ British Columbia, Bioinformat, Vancouver, BC V5Z 4S6, Canada.
84MIT, Dept Math, Cambridge, MA 02142 USA.
85Univ Basel, Dept Psychiat UPK, CH-4002 Basel, Switzerland.
86Univ Basel, Dept Biomed, Human Genom Res Grp, CH-4031 Basel, Switzerland.
87Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Baden Wurttembe, Germany.
88Trinity Coll Dublin, Dept Psychiat, Dublin 8, Ireland.
89Johns Hopkins Univ, Psychiat & Behav Sci, Baltimore, MD 21287 USA.
90QIMR Berghofer Med Res Inst, Genet & Computat Biol, Brisbane, Qld 4006, Australia.
91Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus, Denmark.
92Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
93Rigshosp, Danish Headache Ctr, Dept Neurol, DK-2600 Glostrup, Denmark.
94Mental Hlth Serv Capital Reg Denmark, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, DK-4000 Copenhagen, Denmark.
95Lundbeck Fdn Initiat Psychiat Res, iPSYCH, DK-8000 Copenhagen, Denmark.
96Univ Sydney, Brain & Mind Ctr, Sydney, NSW 2050, Australia.
97Univ Med, Dept Funct Genom, Lnterfac Inst Genet & Funct Genom, D-17489 Greifswald, Mecklenburg Vor, Germany.
98Ernst Moritz Arndt Univ Greifswald, D-17489 Greifswald, Mecklenburg Vor, Germany.
99F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Roche Pharmaceut Res & Early Dev Pharmaceut Sci, CH-4070 Basel, Switzerland.
100Max Planck Inst Psychiat, D-80804 Munich, Germany.
101Kaiser Permanente Northern Calif, Div Res, Oakland, CA 94612 USA.
102Univ Southern Calif, Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
103Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA.
104Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
105Boston Childrens Hosp, Informat Program, Boston, MA 02115 USA.
106Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
107Univ Copenhagen, Herlev Univ Hosp, Dept Endocrinol, DK-2730 Copenhagen, Denmark.
108Univ Hosp Lausanne, Inst Social & Prevent Med IUMSP, CH-1010 Lausanne, Switzerland.
109Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
110Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh EH16 4SB, Midlothian, Scotland.
111NHS 24, Mental Hlth, Glasgow G12 OXH, Lanark, Scotland.
112Univ Bonn, Dept Psychiat & Psychotherapy, D-53105 Bonn, Germany.
113Univ Oxford, Stat, Oxford OX1 3LB, England.
114Columbia Univ Coll Phys & Surg, Psychiat, 630 W 168th St, New York, NY 10032 USA.
115Queensland Univ Technol, Sch Psychol & Counseling, Brisbane, Qld 4059, Australia.
116Childrens Hlth Queensland Hosp & Hlth Serv, IChild & Youth Mental Hlth Serv, South Brisbane, Qld 4000, Australia.
117Univ Queensland, Child Hlth Res Ctr, Brisbane, Qld 4101, Australia.
118Univ Tartu, Estonian Genome Ctr, EE-51005 Tartu, Estonia.
119Univ British Columbia, Med Genet, Vancouver, BC V6H 3N1, Canada.
120Univ British Columbia, Stat, Vancouver, BC V6T 1Z4, Canada.
121Univ Med Greifswald, Univ Med, Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, D-17489 Greifswald, Mecklenburg Vor, Germany.
122Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17489 Greifswald, Mecklenburg Vor, Germany.
123Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia.
124Humus, IS-101 Reykjavik, Iceland.
125Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales.
126Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA.
127Vrije Univ Med Ctr, Clin Genet, NL-1081 HV Amsterdam, Netherlands.
128Vrije Univ Amsterdam, Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.
129Solid Biosci, Boston, MA 02139 USA.
130Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
131Univ Granada, Ctr Biomed Res, Inst Neurosci, Dept Biochem & Mol Biol 2, Granada 18100, Spain.
132Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 RB Groningen, Netherlands.
133Univ Munich, Med Ctr, Dept Psychiat & Psychotherapy, Campus Innenstadt, D-80336 Munich, Germany.
134Univ Munich, Med Ctr, IPPG, Campus Innenstadt, D-80336 Munich, Germany.
135NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
136Kaiser Permanente Washington, Behav Hlth Serv, Seattle, WA 98112 USA.
137Univ Iceland, Dept Psychiat, Fac Med, IS-101 Reykjavik, Iceland.
138James Cook Univ, Sch Med & Dent, Townsville, Qld 4811, Australia.
139Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland.
140Amgen Inc, DeCODE Genet, IS-101 Reykjavik, Iceland.
141Cardiff Univ, Coll Biomed & Life Sci, Cardiff CF14 4EP, S Glam, Wales.
142Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Nordrhein Westf, Germany.
143Univ Med Greifswald, Inst Community Med, D-7489 Greifswald, Mecklenburg Vor, Germany.
144Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.
145Oslo Univ Hosp, Norway Div Mental Hlth & Addict, KG Jebsen Ctr Psychosis Res, N-0407 Oslo, Norway.
146Univ Cambridge, Clin Neurosci, Cambridge CB2 1QW, England.
147Erasmus MC, Internal Med, NL-3015 Rotterdam, Zuid Holland, Netherlands.
148F Hoffmann La Roche Ltd, Neurosci, Ophthalmol & Rare Dis Discovery & Translat Med Ar, Roche Pharmaceut Res & Early Dev, CH-4070 Basel, Switzerland.
149Univ Med Greifswald, Dept Psychiat & Psychotherapy, D-17475 Greifswald, Mecklenburg Vor, Germany.
150Leiden Univ, Med Ctr, Dept Psychiat, NL-2333 ZA Leiden, Netherlands.
151Pfizer Global Res & Dev, Computat Sci Ctr Emphasis, Cambridge, MA 02139 USA.
152Univ Munster, Dept Psychiat, D-48149 Munster, Nordrhein Westf, Germany.
153Univ Basel, Univ Hosp Basel, Inst Med Genet & Pathol, CH-4031 Basel, Switzerland.
154Res Ctr Juelich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany.
155Vrije Univ Med Ctr, Amsterdam Publ Hlth Inst, NL-1081 BT Amsterdam, Netherlands.
156Univ Trento, Ctr Integrat Biol, I-38123 Trento, Trentino Alto A, Italy.
157Univ Freiburg, Fac Med, Med Ctr, Dept Psychiat & Psychotherapy, D-79104 Freiburg, Germany.
158Kaiser Permanente Northern Calif, Psychiat, San Francisco, CA 94115 USA.
159Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
160Univ Toronto, Dept Psychiat, Toronto, ON M5T1R8, Canada.
161Ctr Addict & Mental Hlth, Toronto, ON M6J 1H4, Canada.
162UCL, Div Psychiat, London W1T 7NF, England.
163Janssen Res & Dev LLC, Neurosci Therapeut Area, Titusville, NJ 08560 USA.
164Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
165Aarhus Univ Hosp, Psychosis Res Unit, DK-8200 Aarhus, Denmark.
166Univ Liverpool, Liverpool L69 3BX, Merseyside, England.
167Copenhagen Universt Hosp, Mental Hlth Ctr Copenhagen, DK-2100 Copenhagen, Denmark.
168Pfizer Global Res & Dev, Human Genet & Computat Biomed, Groton, CT 06340 USA.
169Harvard Med Sch, Psychiat, Boston, MA 02215 USA.
170Univ Edinburgh, Med Genet Sect, IGMM, CGEM, Edinburgh EH4 2XU, Midlothian, Scotland.
171Univ Iowa, Psychiat, Iowa City, IA 52246 USA.
172Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
173Univ Med Ctr Gottingen, Dept Psychiat & Psychotherapy, D-37075 Gottingen, Niedersachsen, Germany.
174NIMH, Human Genet Branch, Div Intramural Res Programs, Bethesda, MD 20892 USA.
175Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
176Erasmus MC, Child & Adolescent Psychiat, NL-3015 Rotterdam, Zuid Holland, Netherlands.
177Erasmus MC, Psychiat, NL-3015 Rotterdam, Zuid Holland, Netherlands.
178Dalhousie Univ, Psychiat, Halifax, NS B3H 2E2, Canada.
179New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA.
180Univ Copenhagen, Dept Clin Med, DK-2200 Copenhagen, Denmark.
181Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England.
182Stanford Univ, Psychiat & Behav Sci, Stanford, CA 94305 USA.
183Kings Coll London, NIHR BRC Mental Hlth, London SE5 8AF, England.
184Univ N Carolina, Genet, Chapel Hill, NC 27514 USA.
185Univ N Carolina, Psychiat, Chapel Hill, NC 27514 USA.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020042822784
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-28
Description:

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 10
Article number: 2548
DOI: 10.1038/s41467-019-10461-0
OADOI: https://oadoi.org/10.1038/s41467-019-10461-0
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: This work was supported by the Academy of Finland (E.K., H.L., K.R., and J.L.); University of Helsinki Research Funds (J.L., M.L.P., and H.L.), British Heart Foundation (RMR); Tommy’s (RMR); European Commission (EK, KR, Horizon 2020 Award SC1–2016-RTD-733280 RECAP); NorFace DIAL (E.K., KR PremLife); Foundation for Pediatric Research (E.K.); Juho Vainio Foundation (E.K.); Novo Nordisk Foundation (E.K.); Signe and Ane Gyllenberg Foundation (E.K., K.R.); Sigrid Jusélius Foundation (E.K.); Finnish Medical Foundation (H.L.); Jane and Aatos Erkko Foundation (H.L.); Päivikki and Sakari Sohlberg Foundation (H.L., P.M.V.); the Clinical Graduate school in Pediatrics and Obstetrics/Gynaecology in University of Helsinki (P.M.V.). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1). For this work, MoBa 1 and 2 were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and the Norwegian Research Council/BIOBANK (grant no 221097). This work was also partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The Drakenstein Child Health Study is supported by the Bill and Melinda Gates Foundation (OPP 1017641); with additional support for this work from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NICHD) under Award Number R21HD085849; and the Fogarty International Center (FIC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support for H.J.Z., D.J.S. and N.K., and for research reported in this publication was by the South African Medical Research Council (SAMRC); N.K. receives support from the SAMRC under a Self-Initiated Research Grant. The views and opinions expressed are those of the authors and do not necessarily represent the official views of the SAMRC. This work was also funded by the German Federal Ministry of Education and Research through the Research Consortium Integrated Network IntegraMent (grant 01ZX1314H) under the auspices of the e:Med Programme (NSM). The UCI cohort was supported by a European Research Area Network (ERA Net) Neuron grant (01EW1407A, CB) and National Institutes of Health grant (R01 HD-060628, CB) as well as NIH grant R01 MH-105538 (PDW). This work was also funded by the Canadian Institute for Advanced Research, Child and Brain Development Program, Toronto, ON, Canada (KJOD).
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