Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31186427
TITLE
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.
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.
DATE PUBLISHED
2019 06 11
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/09/13
accepted 2019/05/10
entrez 2019/06/13 06:00
pubmed 2019/06/13 06:00
medline 2019/07/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Czamara D Czamara Darina D Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany.
Eraslan G Eraslan Gökçen G School of Life Sciences, Weihenstephan, Technische Universität München, Freising, 85354, Germany.
Page CM Page Christian M CM Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, 0213, Norway.
Lahti J Lahti Jari J Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00101, Finland.
Lahti-Pulkkinen M Lahti-Pulkkinen Marius M British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Hämäläinen E Hämäläinen Esa E HUSLAB and Department of Clinical Chemistry, Helsinki University, Helsinki, 00290, Finland.
Kajantie E Kajantie Eero E National Institute for Health and Welfare, Helsinki, 00271, Finland.
Laivuori H Laivuori Hannele H Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, 33100, Finland.
Villa PM Villa Pia M PM Medical and Clinical Genetics and Obstetrics and Gynaecology University of Helsinki and Helsinki University Central Hospital, Helsinki, 00014, Finland.
Reynolds RM Reynolds Rebecca M RM British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Nystad W Nystad Wenche W Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, 0213, Norway.
Håberg SE Håberg Siri E SE Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, 0213, Norway.
London SJ London Stephanie J SJ Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, North Carolina, 20814, USA.
O'Donnell KJ O'Donnell Kieran J KJ Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal, H3A 0G4, QC, Canada.
Garg E Garg Elika E Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, H3A 2B4, QC, Canada.
Meaney MJ Meaney Michael J MJ Singapore Institute for Clinical Sciences, Singapore, 117609, Singapore.
Entringer S Entringer Sonja S University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, 92697, USA.
Wadhwa PD Wadhwa Pathik D PD Department of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, 92697, USA.
Buss C Buss Claudia C University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, 92697, USA.
Jones MJ Jones Meaghan J MJ Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
Lin DTS Lin David T S DTS Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
MacIsaac JL MacIsaac Julie L JL Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
Kobor MS Kobor Michael S MS Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
Koen N Koen Nastassja N South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, Cape Town, 7505, South Africa.
Zar HJ Zar Heather J HJ Department of Paediatrics & Child Health and SAMRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, 7505, South Africa.
Koenen KC Koenen Karestan C KC Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
Dalvie S Dalvie Shareefa S Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, 7925, South Africa.
Stein DJ Stein Dan J DJ South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, Cape Town, 7505, South Africa.
Kondofersky I Kondofersky Ivan I Department of Mathematics, Technische Universität München, Munich, 85748, Germany.
Müller NS Müller Nikola S NS Institute of Computational Biology, Helmholtz-Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Theis FJ Theis Fabian J FJ Department of Mathematics, Technische Universität München, Munich, 85748, Germany.
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Räikkönen K Räikkönen Katri K Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Binder EB Binder Elisabeth B EB Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 30329, USA. binder@psych.mpg.de.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Wray Naomi R NR
Ripke Stephan S
Mattheisen Manuel M
Trzaskowski Maciej M
Byrne Enda M EM
Abdellaoui Abdel A
Adams Mark J MJ
Agerbo Esben E
Air Tracy M TM
Andlauer Till F M TFM
Bacanu Silviu-Alin SA
Bækvad-Hansen Marie M
Beekman Aartjan T F ATF
Bigdeli Tim B TB
Blackwood Douglas H R DHR
Bryois Julien J
Buttenschøn Henriette N HN
Bybjerg-Grauholm Jonas J
Cai Na N
Castelao Enrique E
Christensen Jane Hvarregaard JH
Clarke Toni-Kim TK
Coleman Jonathan R I JRI
Colodro-Conde Lucía L
Couvy-Duchesne Baptiste B
Craddock Nick N
Crawford Gregory E GE
Davies Gail G
Deary Ian J IJ
Degenhardt Franziska F
Derks Eske M EM
Direk Nese N
Dolan Conor V CV
Dunn Erin C EC
Eley Thalia C TC
Escott-Price Valentina V
Kiadeh Farnush Farhadi Hassan FFH
Finucane Hilary K HK
Forstner Andreas J AJ
Frank Josef J
Gaspar Héléna A HA
Gill Michael M
Goes Fernando S FS
Gordon Scott D SD
Grove Jakob J
Hall Lynsey S LS
Hansen Christine Søholm CS
Hansen Thomas F TF
Herms Stefan S
Hickie Ian B IB
Hoffmann Per P
Homuth Georg G
Horn Carsten C
Hottenga Jouke-Jan JJ
Hougaard David M DM
Ising Marcus M
Jansen Rick R
Jorgenson Eric E
Knowles James A JA
Kohane Isaac S IS
Kraft Julia J
Kretzschmar Warren W WW
Krogh Jesper J
Kutalik Zoltán Z
Li Yihan Y
Lind Penelope A PA
MacIntyre Donald J DJ
MacKinnon Dean F DF
Maier Robert M RM
Maier Wolfgang W
Marchini Jonathan J
Mbarek Hamdi H
McGrath Patrick P
McGuffin Peter P
Medland Sarah E SE
Mehta Divya D
Middeldorp Christel M CM
Mihailov Evelin E
Milaneschi Yuri Y
Milani Lili L
Mondimore Francis M FM
Montgomery Grant W GW
Mostafavi Sara S
Mullins Niamh N
Nauck Matthias M
Ng Bernard B
Nivard Michel G MG
Nyholt Dale R DR
O'Reilly Paul F PF
Oskarsson Hogni H
Owen Michael J MJ
Painter Jodie N JN
Pedersen Carsten Bøcker CB
Pedersen Marianne Giørtz MG
Peterson Roseann E RE
Pettersson Erik E
Peyrot Wouter J WJ
Pistis Giorgio G
Posthuma Danielle D
Quiroz Jorge A JA
Qvist Per P
Rice John P JP
Riley Brien P BP
Rivera Margarita M
Mirza Saira Saeed SS
Schoevers Robert R
Schulte Eva C EC
Shen Ling L
Shi Jianxin J
Shyn Stanley I SI
Sigurdsson Engilbert E
Sinnamon Grant C B GCB
Smit Johannes H JH
Smith Daniel J DJ
Stefansson Hreinn H
Steinberg Stacy S
Streit Fabian F
Strohmaier Jana J
Tansey Katherine E KE
Teismann Henning H
Teumer Alexander A
Thompson Wesley W
Thomson Pippa A PA
Thorgeirsson Thorgeir E TE
Traylor Matthew M
Treutlein Jens J
Trubetskoy Vassily V
Uitterlinden André G AG
Umbricht Daniel D
Van der Auwera Sandra S
van Hemert Albert M AM
Viktorin Alexander A
Visscher Peter M PM
Wang Yunpeng Y
Webb Bradley T BT
Weinsheimer Shantel Marie SM
Wellmann Jürgen J
Willemsen Gonneke G
Witt Stephanie H SH
Wu Yang Y
Xi Hualin S HS
Yang Jian J
Zhang Futao F
Arolt Volker V
Baune Bernhard T BT
Berger Klaus K
Boomsma Dorret I DI
Cichon Sven S
Dannlowski Udo U
de Geus E J C EJC
DePaulo J Raymond JR
Domenici Enrico E
Domschke Katharina K
Esko Tõnu T
Grabe Hans J HJ
Hamilton Steven P SP
Hayward Caroline C
Heath Andrew C AC
Kendler Kenneth S KS
Kloiber Stefan S
Lewis Glyn G
Li Qingqin S QS
Lucae Susanne S
Madden Pamela A F PAF
Magnusson Patrik K PK
Martin Nicholas G NG
McIntosh Andrew M AM
Metspalu Andres A
Mors Ole O
Mortensen Preben Bo PB
Müller-Myhsok Bertram B
Nordentoft Merete M
Nöthen Markus M MM
O'Donovan Michael C MC
Paciga Sara A SA
Pedersen Nancy L NL
Penninx Brenda W J H BWJH
Perlis Roy H RH
Porteous David J DJ
Potash James B JB
Preisig Martin M
Rietschel Marcella M
Schaefer Catherine C
Schulze Thomas G TG
Smoller Jordan W JW
Stefansson Kari K
Tiemeier Henning H
Uher Rudolf R
Völzke Henry H
Weissman Myrna M MM
Werge Thomas T
Lewis Cathryn M CM
Levinson Douglas F DF
Breen Gerome G
Børglum Anders D AD
Sullivan Patrick F PF
JOURNAL
VOLUME: 10
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2019
MONTH: 06
DAY: 11
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MR/K026992/1 Medical Research Council United Kingdom
U01 MH109536 NIMH NIH HHS United States
G0700704 Medical Research Council United Kingdom
S10 OD018164 NIH HHS United States
MR/L023784/2 Medical Research Council United Kingdom
MR/L010305/1 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Cohort Studies
DNA blood
DNA Methylation genetics
Epigenesis, Genetic genetics
Female genetics
Fetal Blood genetics
Gene-Environment Interaction genetics
Genotype genetics
Humans genetics
Infant, Newborn genetics
Male genetics
Pregnancy genetics
Risk Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
9007-49-2 DNA
OTHER ID's