Genetic Epidemiology, Psychiatric Genetics, Asthma 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
26119815
TITLE
Improving Phenotypic Prediction by Combining Genetic and Epigenetic Associations.
ABSTRACT
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.
DATE PUBLISHED
2015 Jul 2
HISTORY
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
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