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| PMID |
|
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| TITLE |
|
| Genetic and environmental exposures constrain epigenetic drift over the human life course. |
|
| ABSTRACT |
|
|
|
| Epigenetic mechanisms such as DNA methylation (DNAm) are essential for regulation of gene expression. DNAm is dynamic, influenced by both environmental and genetic factors. Epigenetic drift is the divergence of the epigenome as a function of age due to stochastic changes in methylation. Here we show that epigenetic drift may be constrained at many CpGs across the human genome by DNA sequence variation and by lifetime environmental exposures. We estimate repeatability of DNAm at 234,811 autosomal CpGs in whole blood using longitudinal data (2-3 repeated measurements) on 478 older people from two Scottish birth cohorts--the Lothian Birth Cohorts of 1921 and 1936. Median age was 79 yr and 70 yr, and the follow-up period was ∼10 yr and ∼6 yr, respectively. We compare this to methylation heritability estimated in the Brisbane Systems Genomics Study, a cross-sectional study of 117 families (offspring median age 13 yr; parent median age 46 yr). CpG repeatability in older people was highly correlated (0.68) with heritability estimated in younger people. Highly heritable sites had strong underlying cis-genetic effects. Thirty-seven and 1687 autosomal CpGs were associated with smoking and sex, respectively. Both sets were strongly enriched for high repeatability. Sex-associated CpGs were also strongly enriched for high heritability. Our results show that a large number of CpGs across the genome, as a result of environmental and/or genetic constraints, have stable DNAm variation over the human lifetime. Moreover, at a number of CpGs, most variation in the population is due to genetic factors, despite some sites being highly modifiable by the environment. |
| © 2014 Shah et al.; Published by Cold Spring Harbor Laboratory Press. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| aheadofprint |
2014/09/23 |
| entrez |
2014/09/25 06:00 |
| pubmed |
2014/09/25 06:00 |
| medline |
2015/07/21 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Shah S |
|
Shah |
Sonia |
S |
|
Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; |
| McRae AF |
|
McRae |
Allan F |
AF |
|
Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; |
| Marioni RE |
|
Marioni |
Riccardo E |
RE |
|
Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Harris SE |
|
Harris |
Sarah E |
SE |
|
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Gibson J |
|
Gibson |
Jude |
J |
|
Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom; |
| Henders AK |
|
Henders |
Anjali K |
AK |
|
QIMR Berghofer Medical Research Institute, Brisbane, 4029, Queensland, Australia; |
| Redmond P |
|
Redmond |
Paul |
P |
|
Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Cox SR |
|
Cox |
Simon R |
SR |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Pattie A |
|
Pattie |
Alison |
A |
|
Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Corley J |
|
Corley |
Janie |
J |
|
Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Murphy L |
|
Murphy |
Lee |
L |
|
Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom; |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, 4029, Queensland, Australia; |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
QIMR Berghofer Medical Research Institute, Brisbane, 4029, Queensland, Australia; |
| Starr JM |
|
Starr |
John M |
JM |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Wray NR |
|
Wray |
Naomi R |
NR |
|
Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; |
| Deary IJ |
|
Deary |
Ian J |
IJ |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; |
| Visscher PM |
|
Visscher |
Peter M |
PM |
|
Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia peter.visscher@uq.edu.au. |
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 24 |
| ISSUE: 11 |
| TITLE: Genome research |
| ISOABBREVIATION: Genome Res. |
| YEAR: 2014 |
| MONTH: Nov |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1549-5469 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Genome Res |
| COUNTRY: United States |
| ISSNLINKING: 1088-9051 |
| NLMUNIQUEID: 9518021 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| Cites |
Nature. 1993 Nov 25;366(6453):362-5 |
8247133 |
|
| Cites |
Genome Biol. 2011;12(1):R10 |
21251332 |
|
| Cites |
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2545-50 |
9122232 |
|
| Cites |
Cell. 1998 May 1;93(3):305-8 |
9590161 |
|
| Cites |
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3969-74 |
10097147 |
|
| Cites |
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9 |
16009939 |
|
| Cites |
Nat Rev Genet. 2007 Apr;8(4):253-62 |
17363974 |
|
| Cites |
BMC Geriatr. 2007;7:28 |
18053258 |
|
| Cites |
JAMA. 2008 Jun 25;299(24):2877-83 |
18577732 |
|
| Cites |
Nat Genet. 2008 Jul;40(7):904-8 |
18568024 |
|
| Cites |
Cell Stem Cell. 2009 Oct 2;5(4):442-9 |
19796624 |
|
| Cites |
Nat Genet. 2009 Nov;41(11):1207-15 |
19801979 |
|
| Cites |
Am J Hum Genet. 2009 Nov;85(5):750-5 |
19896111 |
|
| Cites |
PLoS Genet. 2010 May;6(5):e1000952 |
20485568 |
|
| Cites |
FASEB J. 2010 Sep;24(9):3135-44 |
20385621 |
|
| Cites |
Adv Genet. 2010;71:3-39 |
20933124 |
|
| Cites |
Nature. 2010 Oct 28;467(7319):1061-73 |
20981092 |
|
| Cites |
Epigenomics. 2011 Jun;3(3):267-77 |
22122337 |
|
| Cites |
Nat Genet. 2012 Jan;44(1):23-31 |
22138693 |
|
| Cites |
PLoS Genet. 2012;8(4):e1002629 |
22532803 |
|
| Cites |
PLoS One. 2012;7(4):e35430 |
22563384 |
|
| Cites |
Epigenetics. 2012 Jan 1;7(1):63-70 |
22207354 |
|
| Cites |
Nat Genet. 2012 Aug;44(8):955-9 |
22820512 |
|
| Cites |
PLoS One. 2012;7(7):e41361 |
22848472 |
|
| Cites |
Genome Res. 2012 Aug;22(8):1395-406 |
22800725 |
|
| Cites |
Am J Hum Genet. 2012 Aug 10;91(2):238-51 |
22883141 |
|
| Cites |
Nat Genet. 2012 Oct;44(10):1084-9 |
22941192 |
|
| Cites |
Environ Health Perspect. 2012 Oct;120(10):1425-31 |
22851337 |
|
| Cites |
BMC Bioinformatics. 2012;13:86 |
22568884 |
|
| Cites |
Int J Epidemiol. 2012 Dec;41(6):1576-84 |
22253310 |
|
| Cites |
Mol Cell. 2013 Jan 24;49(2):359-67 |
23177740 |
|
| Cites |
Hum Mol Genet. 2013 Mar 1;22(5):843-51 |
23175441 |
|
| Cites |
PLoS One. 2013;8(5):e63812 |
23691101 |
|
| Cites |
Am J Hum Genet. 2013 Nov 7;93(5):876-90 |
24183450 |
|
| Cites |
Hum Mol Genet. 2014 Mar 1;23(5):1186-201 |
24163245 |
|
| Cites |
Genome Biol. 2013;14(10):R115 |
24138928 |
|
| Cites |
Bioinformatics. 2014 May 15;30(10):1363-9 |
24478339 |
|
| Cites |
Genome Biol. 2014;15(5):R73 |
24887635 |
|
| Cites |
Am J Hum Genet. 2000 Jan;66(1):279-92 |
10631157 |
|
| Cites |
Mol Cell Biol. 2001 Apr;21(8):2906-17 |
11283268 |
|
| Cites |
Nat Genet. 2002 Jan;30(1):97-101 |
11731797 |
|
| Cites |
J Pers Soc Psychol. 2004 Jan;86(1):130-47 |
14717632 |
|
| Cites |
Nucleic Acids Res. 1988 Feb 11;16(3):1215 |
3344216 |
|
| Cites |
Cell. 1992 Jun 12;69(6):915-26 |
1606615 |
|
| Cites |
BMC Bioinformatics. 2010;11:587 |
21118553 |
|
| Cites |
Epigenetics. 2010 Aug 16;5(6):516-26 |
20505345 |
|
| Cites |
PLoS One. 2011;6(6):e14821 |
21731603 |
|
| Cites |
Nat Genet. 1996 Feb;12(2):205-8 |
8563762 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| BB/F019394/1 |
Biotechnology and Biological Sciences Research Council |
United Kingdom |
| CZB/4/505 |
Chief Scientist Office |
United Kingdom |
| ETM/55 |
Chief Scientist Office |
United Kingdom |
| MR/K026992/1 |
Medical Research Council |
United Kingdom |
|
Biotechnology and Biological Sciences Research Council |
United Kingdom |
|
Chief Scientist Office |
United Kingdom |
|
Medical Research Council |
United Kingdom |
|
Wellcome Trust |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Aged |
|
| Aged, 80 and over |
|
| Algorithms |
|
| Child |
|
| Cohort Studies |
|
| CpG Islands |
genetics |
| Cross-Sectional Studies |
genetics |
| DNA Methylation |
genetics |
| Family Health |
genetics |
| Female |
genetics |
| Gene-Environment Interaction |
genetics |
| Genetics, Population |
methods |
| Genome, Human |
genetics |
| Humans |
genetics |
| Inheritance Patterns |
genetics |
| Male |
genetics |
| Middle Aged |
genetics |
| Models, Genetic |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Sex Factors |
genetics |
| Smoking |
genetics |
| Young Adult |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC4216914 |
NLM |
|
|
