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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight |
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| Author: | Kupers, Leanne K.1,2,3,4; Monnereau, Claire5,6,7; Sharp, Gemma C.1,8; |
| Organizations: |
1Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. 2Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England. 3Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
4Wageningen Univ, Div Human Nutr & Hlth, Wageningen, Netherlands.
5Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands. 6Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands. 7Univ Med Ctr Rotterdam, Dept Pediat, Erasmus MC, Rotterdam, Netherlands. 8Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England. 9Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Childrens Environm Hlth Lab, Berkeley, CA 94720 USA. 10Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, Hanover, NH 03755 USA. 11Bacelona Inst Global Hlth, ISGlobal, Barcelona, Spain. 12Int Agcy Res Canc, Epigenet Grp, Lyon, France. 13Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway. 14Oslo Univ Hosp, Oslo Ctr Biostatisitcs & Epidemol, Oslo, Norway. 15NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Durham, NC USA. 16Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany. 17Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA. 18Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. 19Univ Calif San Francisco, HDF Comprehens Canc Ctr, San Francisco, CA 94143 USA. 20UCSF, Computat Biol & Informat, San Francisco, CA USA. 21North Carolina State Univ, Dept Biol Sci, Raleigh, NC USA. 22North Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC USA. 23Univ Southern Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. 24CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ, Canada. 25Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA. 26Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. 27Univ Southampton, Clin & Expt Sci, Fac Med, Southampton, Hants, England. 28Univ Southampton, Fac Med, Human Dev & Hlth, Southampton Gen Hosp, Southampton, Hants, England. 29Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA. 30Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp,Groningen Res Inst Asthma, Groningen, Netherlands. 31Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. 32Univ Western Australia, Telethon Kids Inst, Perth, WA, Australia. 33Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD GRIAC, Groningen, Netherlands. 34Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England. 35Karolinska Inst, Inst Environm Med, Stockholm, Sweden. 36Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. 37Univ Helsinki, Helsinki Coll Adv Studies, Helsinki, Finland. 38Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland. 39Vrije Univ Amsterdam, Netherlands Twin Register, Dept Biol Psychol, Amsterdam, Netherlands. 40VITO Hlth, Mol, Belgium. 41Hasselt Univ, Fac Sci, Theoret Phys, Hasselt, Belgium. 42Hasselt Univ, Ctr Environm Sci, Hasselt, Belgium. 43Univ Southern Denmark, Dept Clin Res, Res Unit Gynaecol & Obstet, Odense, Denmark. 44Univ Med Ctr Rotterdam, Dept Pediat, Div Resp Med & Allergol, Erasmus MC, Rotterdam, Netherlands. 45Univ Med Ctr Rotterdam, Dept Pediat, Div Neonatol, Erasmus MC, Rotterdam, Netherlands. 46NIEHS, Biostat & Computat Biol Branch, NIH, Durham, NC USA. 47Univ Colorado, Colorado Sch Publ Hlth, Dept Biostat & Informat, Anschutz Med Campus, Aurora, CO USA. 48Hasselt Univ, Ctr Environm Sci, Diepenbeek, Belgium. 49Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, St Marys Campus,Norfolk Pl, London, England. 50Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. 51North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. 52Ctr Genom Regulat CRG, Bioinformat & Genom Program, Barcelona, Spain. 53UPF, Barcelona, Spain. 54CIBERESP, Barcelona, Spain. 55Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada. 56Univ Calif Davis, MIND Inst, Sch Med, Dept Publ Hlth Sci, Sacramento, CA 95817 USA. 57Univ Memphis, Sch Publ Hlth, Div Epidemiol Biostat & Environm Hlth, Memphis, TN 38152 USA. 58Childrens Environm Hlth & Dis Prevent Res Ctr Dar, Hanover, NH USA. 59Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. 60Univ Western Australia, Med Sch, Perth, WA, Australia. 61Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu 90014, Finland. 62Univ Oulu, Bioctr Oulu, Oulu, Finland. 63Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. 64Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden. 65Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. 66Univ Helsinki, Obstet & Gynaecol, Helsinki, Finland. 67Helsinki Univ Hosp, Helsinki, Finland. 68Gambia London Sch Hyg & Trop Med, Med Res Council Unit, London, England. 69Kings Coll London, Dept Women & Childrens Hlth, London, England. 70Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. 71Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Sect Epidemiol, Copenhagen, Denmark. 72Univ Colorado, Div Biomed Informat & Personalized Med, Dept Med, Anschutz Med Campus, Aurora, CO USA. 73Leuven Univ, Dept Publ Hlth & Primary Care, Leuven, Belgium. 74Univ Leeds, Sch Food Sci & Nutr, Leeds, W Yorkshire, England. 75Univ Turin, Dept Med Sci, Turin, Italy. 76AOU Citta Salute & Sci, CPO Piemonte, Turin, Italy. 77IMIM Hosp del Mar Med Res Inst, Barcelona, Spain. 78Univ Calif Berkeley, Sch Publ Hlth, Ctr Environm Res & Childrens Hlth, Berkeley, CA 94720 USA. 79Vrije Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Biol Psychol, Amsterdam, Netherlands. 80Duke Univ, Med Ctr, Dept Community & Family Med, Raleigh, NC USA. 81Univ Oxford, George Inst Global Hlth, Nuffield Dept Womens & Reprod Hlth, Oxford, England. 82Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ, Canada. 83Chicoutimi Hosp, ECOGENE Biocluster 21, Saguenay, PQ, Canada. 84Columbia Univ, Mailman Sch Publ Hlth, Lab Precis Environm Biosci, New York, NY USA. 85Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. 86Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. 87Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England. 88Folkhalsan Inst Genet, Helsinki, Finland. 89Univ Helsinki, Res Programs Unit, Mol Neurol, Helsinki, Finland. 90Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden. 91Kings Coll London, Guys Hosp, Sch Basic & Med Biosci, London, England. 92David Hide Asthma & Allergy Res Ctr, Newport, Wight, England. 93Univ Helsinki, HUSLAB, Helsinki, Finland. 94Univ Helsinki, Dept Clin Chem, Helsinki, Finland. 95Univ Leeds, Sch Med, LICAMM, Leeds, W Yorkshire, England. 96Vrije Univ Amsterdam, Amsterdam Publ Hlth Inst, Amsterdam, Netherlands. 97Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MA USA. 98Drexel Univ, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. 99Univ Leuven, KU Leuven, Dept Neurosci Expt Neurol, Leuven, Belgium. 100Univ Leuven, KU Leuven, LIND, Leuven, Belgium. 101VIB, Lab Neurobiol, Ctr Brain & Dis Res, Leuven, Belgium. 102Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. 103Sachs Childrens 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Oslo, Norway. 119Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. 120Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. 121Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. 122Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. 123Norwegian Inst Publ Hlth, Dept Noncommunicable Dis, Oslo, Norway. |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 12.5 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2020042822771 |
| Language: | English |
| Published: |
Springer Nature,
2019
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| Publish Date: | 2020-04-28 |
| Description: |
AbstractBirthweight 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. see all
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| Series: |
Nature communications |
| ISSN: | 2041-1723 |
| ISSN-E: | 2041-1723 |
| ISSN-L: | 2041-1723 |
| Volume: | 10 |
| Article number: | 1893 |
| DOI: | 10.1038/s41467-019-09671-3 |
| OADOI: | https://oadoi.org/10.1038/s41467-019-09671-3 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3111 Biomedicine |
| Subjects: | |
| Funding: |
For all studies, funding statements can be found in Supplementary Information: Supplementary Funding. |
| Copyright information: |
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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https://creativecommons.org/licenses/by/4.0/ |