Abstract

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.

Details

Title
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Author
Küpers, Leanne K 1 ; Monnereau Claire 2 ; Sharp, Gemma C 3   VIAFID ORCID Logo  ; Yousefi, Paul 4 ; Salas, Lucas A 5   VIAFID ORCID Logo  ; Ghantous Akram 6 ; Page, Christian M 7 ; Reese, Sarah E 8 ; Wilcox, Allen J 8 ; Czamara Darina 9   VIAFID ORCID Logo  ; Starling, Anne P 10 ; Novoloaca Alexei 6 ; Lent, Samantha 11 ; Roy, Ritu 12 ; Hoyo Cathrine 13 ; Breton, Carrie V 14 ; Allard, Catherine 15   VIAFID ORCID Logo  ; Just, Allan C 16 ; Bakulski, Kelly M 17   VIAFID ORCID Logo  ; Holloway, John W 18   VIAFID ORCID Logo  ; Everson, Todd M 19 ; Cheng-Jian, Xu 20   VIAFID ORCID Logo  ; Rae-Chi, Huang 21 ; van der Plaat Diana A 22 ; Wielscher Matthias 23 ; Merid Simon Kebede 24 ; Vilhelmina, Ullemar 25 ; Rezwan, Faisal I 26   VIAFID ORCID Logo  ; Lahti Jari 27   VIAFID ORCID Logo  ; van Dongen Jenny 28   VIAFID ORCID Logo  ; Langie Sabine A S 29 ; Richardson, Tom G 30   VIAFID ORCID Logo  ; Magnus, Maria C 31 ; Nohr, Ellen A 32 ; Xu, Zongli 33 ; Duijts Liesbeth 34 ; Zhao, Shanshan 35 ; Zhang, Weiming 36 ; Plusquin Michelle 37 ; DeMeo, Dawn L 38 ; Solomon, Olivia 39 ; Heimovaara, Joosje H 40 ; Jima, Dereje D 41 ; Gao, Lu 14 ; Bustamante Mariona 42 ; Perron, Patrice 43 ; Wright, Robert O 16 ; Hertz-Picciotto Irva 44 ; Zhang, Hongmei 45 ; Karagas, Margaret R 46 ; Gehring Ulrike 47 ; Marsit, Carmen J 19   VIAFID ORCID Logo  ; Beilin, Lawrence J 48 ; Vonk, Judith M 22 ; Jarvelin Marjo-Riitta 49 ; Bergström, Anna 50 ; Örtqvist, Anne K 25 ; Ewart, Susan 51 ; Villa, Pia M 52 ; Moore, Sophie E 53 ; Willemsen Gonneke 28 ; Standaert Arnout R L 54 ; Håberg, Siri E 55 ; Sørensen Thorkild I A 56   VIAFID ORCID Logo  ; Taylor, Jack A 8 ; Räikkönen Katri 57 ; Yang, Ivana V 58 ; Kechris Katerina 59 ; Nawrot, Tim S 60 ; Silver, Matt J 61   VIAFID ORCID Logo  ; Gong, Yun Yun 62 ; Richiardi Lorenzo 63 ; Kogevinas Manolis 64 ; Litonjua, Augusto A 65 ; Eskenazi, Brenda 66 ; Huen, Karen 67 ; Mbarek Hamdi 68   VIAFID ORCID Logo  ; Maguire, Rachel L 69 ; Dwyer, Terence 70 ; Vrijheid Martine 71 ; Bouchard, Luigi 72 ; Baccarelli, Andrea A 73 ; Croen Lisa A 74   VIAFID ORCID Logo  ; Karmaus Wilfried 45 ; Anderson, Denise 21   VIAFID ORCID Logo  ; de Vries Maaike 22 ; Sebert Sylvain 75 ; Kere Juha 76   VIAFID ORCID Logo  ; Karlsson, Robert 25   VIAFID ORCID Logo  ; Arshad Syed Hasan 77 ; Hämäläinen Esa 78 ; Routledge, Michael N 79 ; Boomsma Dorret I 80 ; Feinberg, Andrew P 81   VIAFID ORCID Logo  ; Newschaffer, Craig J 82 ; Govarts Eva 54 ; Moisse Matthieu 83   VIAFID ORCID Logo  ; Daniele, Fallin M 84 ; Melén Erik 85 ; Prentice, Andrew M 61 ; Kajantie Eero 86 ; Almqvist Catarina 87 ; Oken, Emily 88 ; Dabelea Dana 89 ; Marike, Boezen H 22 ; Melton, Phillip E 90   VIAFID ORCID Logo  ; Wright, Rosalind J 16 ; Koppelman, Gerard H 91 ; Trevisi Letizia 92 ; Marie-France, Hivert 93 ; Sunyer Jordi 64 ; Munthe-Kaas, Monica C 94 ; Murphy, Susan K 95 ; Corpeleijn Eva 40 ; Wiemels, Joseph 96 ; Holland, Nina 67 ; Herceg Zdenko 6 ; Binder, Elisabeth B 97 ; Davey Smith George 30   VIAFID ORCID Logo  ; Jaddoe, Vincent W, V 2   VIAFID ORCID Logo  ; Lie, Rolv T 98 ; Nystad Wenche 99 ; London, Stephanie J 8   VIAFID ORCID Logo  ; Lawlor, Debbie A 30   VIAFID ORCID Logo  ; Relton, Caroline L 30 ; Snieder Harold 40 ; Felix, Janine F 2   VIAFID ORCID Logo 

1  University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University Medical Center Groningen, Department of Epidemiology, University of Groningen, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598); Wageningen University, Division of Human Nutrition and Health, Wageningen, The Netherlands (GRID:grid.4818.5) (ISNI:0000 0001 0791 5666) 
2  University Medical Center Rotterdam, The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); University Medical Center Rotterdam, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); University Medical Center Rotterdam, Department of Pediatrics, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
3  University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, School of Oral and Dental Sciences, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
4  University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of California, Children’s Environmental Health Laboratory, Division of Environmental Health Sciences, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878) 
5  Geisel School of Medicine at Dartmouth College, Department of Epidemiology, Hanover, USA (GRID:grid.254880.3) (ISNI:0000 0001 2179 2404); ISGlobal, Bacelona Institute for Global Health, Barcelona, Spain (GRID:grid.434607.2) (ISNI:0000 0004 1763 3517) 
6  Epigenetics Group, International Agency for Research on Cancer, Lyon, France (GRID:grid.17703.32) (ISNI:0000000405980095) 
7  Norwegian Institute of Public Health, Centre for Fertility and Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204); Oslo University Hospital, Oslo Centre for Biostatisitcs and Epidemology, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
8  Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Service, Research Triangle Park, Durham, USA (GRID:grid.280664.e) (ISNI:0000 0001 2110 5790) 
9  Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095) 
10  University of Colorado Anschutz Medical Campus, Department of Epidemiology, Colorado School of Public Health, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) 
11  Boston University School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
12  University of California, HDF Comprehensive Cancer Center, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811); Computational Biology and Informatics, UCSF, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
13  North Carolina State University, Department of Biological Sciences, Raleigh, USA (GRID:grid.40803.3f) (ISNI:0000 0001 2173 6074); North Carolina State University, Center for Human Health and the Environment, Raleigh, USA (GRID:grid.40803.3f) (ISNI:0000 0001 2173 6074) 
14  University of Southern California, Department of Preventive Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
15  Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Canada (GRID:grid.411172.0) (ISNI:0000 0001 0081 2808) 
16  Icahn School of Medicine at Mount Sinai, Department of Environmental Medicine and Public Health, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
17  University of Michigan, Department of Epidemiology, School of Public Health, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
18  University of Southampton, Clinical and Experimental Sciences, Faculty of Medicine, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297); University of Southampton, Southampton General Hospital, Human Development and Health, Faculty of Medicine, Southampton, UK (GRID:grid.5491.9) 
19  Rollins School of Public Health at Emory University, Department of Environmental Health, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
20  University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598); University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
21  University of Western Australia, Telethon Kids Institute, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
22  University Medical Center Groningen, Department of Epidemiology and Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
23  School of Public Health, Imperial College London, Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
24  Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
25  Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
26  University of Southampton, Southampton General Hospital, Human Development and Health, Faculty of Medicine, Southampton, UK (GRID:grid.4714.6) 
27  University of Helsinki, Helsinki Collegium for Advanced Studies, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); University of Helsinki, Department of Psychology and Logopedics, Faculty of Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
28  Vrije Universiteit Amsterdam, Department of Biological Psychology, Netherlands Twin Register, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
29  VITO - Health, Mol, Belgium (GRID:grid.6717.7) (ISNI:0000000120341548); Hasselt University, Theoretical Physics, Faculty of Sciences, Hasselt, Belgium (GRID:grid.12155.32) (ISNI:0000 0001 0604 5662); Hasselt University, Centre for Environmental Sciences, Hasselt, Belgium (GRID:grid.12155.32) (ISNI:0000 0001 0604 5662) 
30  University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
31  University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); Norwegian Institute of Public Health, Centre for Fertility and Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204) 
32  University of Southern Denmark, Research Unit for Gynaecology and Obstetrics, Department of Clinical Research, Odense, Denmark (GRID:grid.10825.3e) (ISNI:0000 0001 0728 0170) 
33  University Medical Center Rotterdam, Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
34  Wageningen University, Division of Human Nutrition and Health, Wageningen, The Netherlands (GRID:grid.4818.5) (ISNI:0000 0001 0791 5666); University Medical Center Rotterdam, Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); University Medical Center Rotterdam, Department of Pediatrics, Division of Neonatology, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
35  National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Biostatistics and Computational Biology Branch, Durham, USA (GRID:grid.280664.e) (ISNI:0000 0001 2110 5790) 
36  University of Colorado Anschutz Medical Campus, Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) 
37  Hasselt University, Centre for Environmental Sciences, Diepenbeek, Belgium (GRID:grid.12155.32) (ISNI:0000 0001 0604 5662); MRC/PHE Centre for Environment and Health School of Public Health Imperial College London, St Mary’s Campus, Norfolk Place, London, UK (GRID:grid.14105.31) (ISNI:0000000122478951) 
38  Brigham and Women’s Hospital, Harvard Medical School, Channing Division of Network Medicine, Boston, USA (GRID:grid.14105.31) 
39  University of Bristol, School of Oral and Dental Sciences, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
40  University Medical Center Groningen, Department of Epidemiology, University of Groningen, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
41  North Carolina State University, Center for Human Health and the Environment, Raleigh, USA (GRID:grid.40803.3f) (ISNI:0000 0001 2173 6074); North Carolina State University, Bioinformatics Research Center, Raleigh, USA (GRID:grid.40803.3f) (ISNI:0000 0001 2173 6074) 
42  ISGlobal, Bacelona Institute for Global Health, Barcelona, Spain (GRID:grid.434607.2) (ISNI:0000 0004 1763 3517); Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), Barcelona, Spain (GRID:grid.11478.3b); Universitat Pompeu Fabra (UPF), Barcelona, Spain (GRID:grid.5612.0) (ISNI:0000 0001 2172 2676); CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427) 
43  Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Canada (GRID:grid.411172.0) (ISNI:0000 0001 0081 2808); Universite de Sherbrooke, Department of Medicine, Sherbrooke, Canada (GRID:grid.86715.3d) (ISNI:0000 0000 9064 6198) 
44  University of California Davis MIND Institute, Department of Public Health Sciences, School of Medicine, Sacramento, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
45  University of Memphis, Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, Memphis, USA (GRID:grid.56061.34) (ISNI:0000 0000 9560 654X) 
46  Geisel School of Medicine at Dartmouth College, Department of Epidemiology, Hanover, USA (GRID:grid.254880.3) (ISNI:0000 0001 2179 2404); Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, USA (GRID:grid.254880.3) 
47  Utrecht University, Institute for Risk Assessment Sciences, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234) 
48  University of Western Australia, Medical School, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
49  School of Public Health, Imperial College London, Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University of Oulu, Center for Life Course Health Research, Faculty of Medicine, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); University of Oulu, Biocenter Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); Oulu University Hospital, Unit of Primary Care, Oulu, Finland (GRID:grid.412326.0) (ISNI:0000 0004 4685 4917) 
50  Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Stockholm County Council, Center for Occupational and Environmental Medicine, Stockholm, Sweden (GRID:grid.425979.4) (ISNI:0000 0001 2326 2191) 
51  Michigan State University, College of Veterinary Medicine, East Lansing, USA (GRID:grid.17088.36) (ISNI:0000 0001 2150 1785) 
52  University of Helsinki and Helsinki University Hospital, Obstetrics and Gynaecology, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
53  Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X); King’s College London, Department of Women and Children’s Health, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
54  VITO - Health, Mol, Belgium (GRID:grid.6717.7) (ISNI:0000000120341548) 
55  Norwegian Institute of Public Health, Centre for Fertility and Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204) 
56  University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); University of Copenhagen, Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
57  University of Helsinki, Department of Psychology and Logopedics, Faculty of Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
58  University of Colorado Anschutz Medical Campus, Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) 
59  University Medical Center Rotterdam, Department of Pediatrics, Division of Neonatology, Erasmus MC, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
60  Hasselt University, Centre for Environmental Sciences, Diepenbeek, Belgium (GRID:grid.12155.32) (ISNI:0000 0001 0604 5662); Leuven University, Department of Public Health & Primary Care, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) 
61  Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
62  University of Leeds, School of Food Sciences and Nutrition, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403) 
63  University of Turin, Department of Medical Sciences, Turin, Italy (GRID:grid.7605.4) (ISNI:0000 0001 2336 6580); AOU Citta della Salute e della Sceinza, CPO Piemonte, Turin, Italy (GRID:grid.420240.0) (ISNI:0000 0004 1756 876X) 
64  ISGlobal, Bacelona Institute for Global Health, Barcelona, Spain (GRID:grid.434607.2) (ISNI:0000 0004 1763 3517); Universitat Pompeu Fabra (UPF), Barcelona, Spain (GRID:grid.5612.0) (ISNI:0000 0001 2172 2676); CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (GRID:grid.411142.3) (ISNI:0000 0004 1767 8811) 
65  Brigham and Women’s Hospital, Harvard Medical School, Channing Division of Network Medicine, Boston, USA (GRID:grid.411142.3) 
66  University of California, Children’s Environmental Health Laboratory, Division of Environmental Health Sciences, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); University of California, Center for Environmental Research and Children’s Health, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878) 
67  University of California, Children’s Environmental Health Laboratory, Division of Environmental Health Sciences, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878) 
68  Vrije Universiteit Amsterdam, Department of Biological Psychology, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
69  North Carolina State University, Department of Biological Sciences, Raleigh, USA (GRID:grid.40803.3f) (ISNI:0000 0001 2173 6074); Duke University Medical Center, Department of Community and Family Medicine, Raleigh, USA (GRID:grid.189509.c) (ISNI:0000000100241216) 
70  University of Oxford, The George Institute for Global Health, Nuffield Department of Women’s & Reproductive Health, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
71  ISGlobal, Bacelona Institute for Global Health, Barcelona, Spain (GRID:grid.434607.2) (ISNI:0000 0004 1763 3517); Universitat Pompeu Fabra (UPF), Barcelona, Spain (GRID:grid.5612.0) (ISNI:0000 0001 2172 2676); CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427) 
72  Université de Sherbrooke, Department of Biochemistry, Sherbrooke, Canada (GRID:grid.86715.3d) (ISNI:0000 0000 9064 6198); Chicoutimi Hospital, ECOGENE-21 Biocluster, Saguenay, Canada (GRID:grid.86715.3d) 
73  Columbia University Mailman School of Public Health, Laboratory of Precision Environmental Biosciences, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729); Columbia University, Department of Environmental Health Sciences, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
74  Division of Research, Kaiser Permanente Northern California, Oakland, USA (GRID:grid.280062.e) (ISNI:0000 0000 9957 7758) 
75  University of Oulu, Center for Life Course Health Research, Faculty of Medicine, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); University of Oulu, Biocenter Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); School of Public Health, Imperial College London, Department for Genomics of Common Diseases, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
76  University of Helsinki, Folkhälsan Institute of Genetics, Helsinki, and Research Programs Unit, Molecular Neurology, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); King’s College London, Guy’s Hospital, School of Basic and Medical Biosciences, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
77  University of Southampton, Clinical and Experimental Sciences, Faculty of Medicine, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297); David Hide Asthma and Allergy Research Centre, Isle of Wight, UK (GRID:grid.5491.9) 
78  University of Helsinki, HUSLAB and the Department of Clinical Chemistry, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
79  LICAMM, School of Medicine, Univeristy of Leeds, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403) 
80  Vrije Universiteit Amsterdam, Department of Biological Psychology, Netherlands Twin Register, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Vrije Universiteit Amsterdam, Amsterdam Public Health Institute, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
81  Johns Hopkins University School of Medicine, Center for Epigenetics, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
82  Drexel University, AJ Drexel Autism Institute, Philadelphia, USA (GRID:grid.166341.7) (ISNI:0000 0001 2181 3113) 
83  KU Leuven – University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Institute for Neuroscience and Disease (LIND), Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium (GRID:grid.11486.3a) (ISNI:0000000104788040) 
84  Johns Hopkins University, Department of Mental Health, Bloomberg School of Public Health, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
85  Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Sachs’ Children’s Hospital, Stockholm, Sweden (GRID:grid.416452.0) 
86  National Institute for Health and Welfare, Helsinki and Oulu, Oulu, Finland (GRID:grid.14758.3f) (ISNI:0000 0001 1013 0499); Helsinki University Hospital and University of Helsinki, Hospital for Children and Adolescents, Helsinki, Finland (GRID:grid.15485.3d) (ISNI:0000 0000 9950 5666); Oulu University Hospital and University of Oulu, PEDEGO Research Unit, MRC Oulu, Oulu, Finland (GRID:grid.412326.0) (ISNI:0000 0004 4685 4917) 
87  Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Karolinska University Hospital, Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children’s Hospital, Stockholm, Sweden (GRID:grid.24381.3c) (ISNI:0000 0000 9241 5705) 
88  Harvard Pilgrim Health Care Institute, Department of Population Medicine, Harvard Medical School, Boston, USA (GRID:grid.67104.34) (ISNI:0000 0004 0415 0102) 
89  University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Department of Epidemiology, Colorado School of Public Health, and Department of Pediatrics, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X) 
90  University of Western Australia, Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Curtin University, School of Pharmacy and Biomedical Sciences, Perth, Australia (GRID:grid.1032.0) (ISNI:0000 0004 0375 4078) 
91  University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
92  Harvard Medical School, Department of Global Health and Social Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
93  Universite de Sherbrooke, Department of Medicine, Sherbrooke, Canada (GRID:grid.86715.3d) (ISNI:0000 0000 9064 6198); Harvard Pilgrim Health Care Institute, Department of Population Medicine, Harvard Medical School, Boston, USA (GRID:grid.67104.34) (ISNI:0000 0004 0415 0102); Diabetes Unit, Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
94  Norwegian Institute of Public Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204); Oslo University Hospital, Department of Pediatric Oncology and Hematology, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
95  Duke University Medical Center, Department of Obstetrics and Gynecology, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216) 
96  University of California, Department of Epidemiology and Biostatistics, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
97  Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095); Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Altanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
98  Norwegian Institute of Public Health, Centre for Fertility and Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204); University of Bergen, Department of Global Public Health and Primary Care, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443) 
99  Norwegian Institute for Public Health, Department for Non-Communicable Diseases, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-09671-3
ProQuest document ID
2393006665
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.