|
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| PMID |
|
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| TITLE |
|
| Improving Phenotypic Prediction by Combining Genetic and Epigenetic Associations. |
|
| ABSTRACT |
|
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|
| We tested whether DNA-methylation profiles account for inter-individual variation in body mass index (BMI) and height and whether they predict these phenotypes over and above genetic factors. Genetic predictors were derived from published summary results from the largest genome-wide association studies on BMI (n ∼ 350,000) and height (n ∼ 250,000) to date. We derived methylation predictors by estimating probe-trait effects in discovery samples and tested them in external samples. Methylation profiles associated with BMI in older individuals from the Lothian Birth Cohorts (LBCs, n = 1,366) explained 4.9% of the variation in BMI in Dutch adults from the LifeLines DEEP study (n = 750) but did not account for any BMI variation in adolescents from the Brisbane Systems Genetic Study (BSGS, n = 403). Methylation profiles based on the Dutch sample explained 4.9% and 3.6% of the variation in BMI in the LBCs and BSGS, respectively. Methylation profiles predicted BMI independently of genetic profiles in an additive manner: 7%, 8%, and 14% of variance of BMI in the LBCs were explained by the methylation predictor, the genetic predictor, and a model containing both, respectively. The corresponding percentages for LifeLines DEEP were 5%, 9%, and 13%, respectively, suggesting that the methylation profiles represent environmental effects. The differential effects of the BMI methylation profiles by age support previous observations of age modulation of genetic contributions. In contrast, methylation profiles accounted for almost no variation in height, consistent with a mainly genetic contribution to inter-individual variation. The BMI results suggest that combining genetic and epigenetic information might have greater utility for complex-trait prediction. |
| Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2015/03/31 |
| accepted |
2015/05/21 |
| aheadofprint |
2015/06/25 |
| entrez |
2015/06/30 06:00 |
| pubmed |
2015/06/30 06:00 |
| medline |
2015/09/26 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Shah S |
|
Shah |
Sonia |
S |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia; University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD 4072, Australia. |
| Bonder MJ |
|
Bonder |
Marc J |
MJ |
|
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, the Netherlands. |
| Marioni RE |
|
Marioni |
Riccardo E |
RE |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. |
| Zhu Z |
|
Zhu |
Zhihong |
Z |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia. |
| McRae AF |
|
McRae |
Allan F |
AF |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia; University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD 4072, Australia. |
| Zhernakova A |
|
Zhernakova |
Alexandra |
A |
|
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, the Netherlands. |
| Harris SE |
|
Harris |
Sarah E |
SE |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. |
| Liewald D |
|
Liewald |
Dave |
D |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. |
| Henders AK |
|
Henders |
Anjali K |
AK |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. |
| Mendelson MM |
|
Mendelson |
Michael M |
MM |
|
Framingham Heart Study and Boston University School of Medicine, Boston, MA 01702, USA; Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA; Population Studies Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892-7936, USA. |
| Liu C |
|
Liu |
Chunyu |
C |
|
Department of Biostatistics, Boston University, Boston, MA 02118, USA. |
| Joehanes R |
|
Joehanes |
Roby |
R |
|
Hebrew Senior Life, Harvard Medical School, Boston, MA 02131, USA. |
| Liang L |
|
Liang |
Liming |
L |
|
Departments of Epidemiology and Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA. |
|
BIOS Consortium |
|
|
|
|
|
| Levy D |
|
Levy |
Daniel |
D |
|
Population Studies Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892-7936, USA. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. |
| Starr JM |
|
Starr |
John M |
JM |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. |
| Wijmenga C |
|
Wijmenga |
Cisca |
C |
|
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, the Netherlands. |
| Wray NR |
|
Wray |
Naomi R |
NR |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia. |
| Yang J |
|
Yang |
Jian |
J |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. |
| Franke L |
|
Franke |
Lude |
L |
|
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, the Netherlands. |
| Deary IJ |
|
Deary |
Ian J |
IJ |
|
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. |
| Visscher PM |
|
Visscher |
Peter M |
PM |
|
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia; University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD 4072, Australia; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. Electronic address: peter.visscher@uq.edu.au. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Heijmans |
Bastiaan T |
BT |
|
| 't Hoen |
Peter A C |
PA |
|
| van Meurs |
Joyce |
J |
|
| Isaacs |
Aaron |
A |
|
| Jansen |
Rick |
R |
|
| Franke |
Lude |
L |
|
| Boomsma |
Dorret I |
DI |
|
| Pool |
René |
R |
|
| van Dongen |
Jenny |
J |
|
| Hottenga |
Jouke J |
JJ |
|
| van Greevenbroek |
Marleen M J |
MM |
|
| Stehouwer |
Coen D A |
CD |
|
| van der Kallen |
Carla J H |
CJ |
|
| Schalkwijk |
Casper G |
CG |
|
| Wijmenga |
Cisca |
C |
|
| Zhernakova |
Sasha |
S |
|
| Tigchelaar |
Ettje F |
EF |
|
| Slagboom |
P Eline |
PE |
|
| Beekman |
Marian |
M |
|
| Deelen |
Joris |
J |
|
| van Heemst |
Diana |
D |
|
| Veldink |
Jan H |
JH |
|
| van den Berg |
Leonard H |
LH |
|
| van Duijn |
Cornelia M |
CM |
|
| Hofman |
Bert A |
BA |
|
| Uitterlinden |
André G |
AG |
|
| Jhamai |
P Mila |
PM |
|
| Verbiest |
Michael |
M |
|
| Suchiman |
H Eka D |
HE |
|
| Verkerk |
Marijn |
M |
|
| van der Breggen |
Ruud |
R |
|
| van Rooij |
Jeroen |
J |
|
| Lakenberg |
Nico |
N |
|
| Mei |
Hailiang |
H |
|
| van Iterson |
Maarten |
M |
|
| van Galen |
Michiel |
M |
|
| Bot |
Jan |
J |
|
| van 't Hof |
Peter |
P |
|
| Deelen |
Patrick |
P |
|
| Nooren |
Irene |
I |
|
| Moed |
Matthijs |
M |
|
| Vermaat |
Martijn |
M |
|
| Zhernakova |
Dasha V |
DV |
|
| Luijk |
René |
R |
|
| Bonder |
Marc Jan |
MJ |
|
| van Dijk |
Freerk |
F |
|
| Arindrarto |
Wibowo |
W |
|
| Kielbasa |
Szymon M |
SM |
|
| Swertz |
Morris A |
MA |
|
| van Zwet |
Erik W |
EW |
|
|
| JOURNAL |
|
| VOLUME: 97 |
| ISSUE: 1 |
| TITLE: American journal of human genetics |
| ISOABBREVIATION: Am. J. Hum. Genet. |
| YEAR: 2015 |
| MONTH: Jul |
| DAY: 2 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1537-6605 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Am J Hum Genet |
| COUNTRY: United States |
| ISSNLINKING: 0002-9297 |
| NLMUNIQUEID: 0370475 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Validation Studies |
|
| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| BB/F019394/1 |
Biotechnology and Biological Sciences Research Council |
United Kingdom |
| MR/K026992/1 |
Medical Research Council |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Analysis of Variance |
|
| Body Height |
genetics |
| Body Mass Index |
genetics |
| Cohort Studies |
genetics |
| DNA Methylation |
genetics |
| Genome-Wide Association Study |
methods |
| Genotype |
methods |
| Humans |
methods |
| Middle Aged |
methods |
| Models, Genetic |
methods |
| Netherlands |
methods |
| Obesity |
genetics |
| Phenotype |
genetics |
| Scotland |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC4572498 |
NLM |
|
|
