|
|
| PMID |
|
|
| 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 |
|
|
| 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 |
|
|
|
