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.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
29500431
TITLE
Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits.
ABSTRACT
The identification of genes and regulatory elements underlying the associations discovered by GWAS is essential to understanding the aetiology of complex traits (including diseases). Here, we demonstrate an analytical paradigm of prioritizing genes and regulatory elements at GWAS loci for follow-up functional studies. We perform an integrative analysis that uses summary-level SNP data from multi-omics studies to detect DNA methylation (DNAm) sites associated with gene expression and phenotype through shared genetic effects (i.e., pleiotropy). We identify pleiotropic associations between 7858 DNAm sites and 2733 genes. These DNAm sites are enriched in enhancers and promoters, and >40% of them are mapped to distal genes. Further pleiotropic association analyses, which link both the methylome and transcriptome to 12 complex traits, identify 149 DNAm sites and 66 genes, indicating a plausible mechanism whereby the effect of a genetic variant on phenotype is mediated by genetic regulation of transcription through DNAm.
DATE PUBLISHED
2018 Mar 02
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/08/17
accepted 2018/02/07
entrez 2018/03/04 06:00
pubmed 2018/03/04 06:00
medline 2018/03/04 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wu Y Wu Yang Y Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Zeng J Zeng Jian J Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Zhang F Zhang Futao F Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Zhu Z Zhu Zhihong Z Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Qi T Qi Ting T Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Zheng Z Zheng Zhili Z The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Lloyd-Jones LR Lloyd-Jones Luke R LR Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Marioni RE Marioni Riccardo E RE Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
Martin NG Martin Nicholas G NG Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
Wray NR Wray Naomi R NR Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
Visscher PM Visscher Peter M PM Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
McRae AF McRae Allan F AF Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Yang J Yang Jian J Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia. jian.yang@uq.edu.au.
INVESTIGATORS
JOURNAL
VOLUME: 9
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2018
MONTH: Mar
DAY: 02
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
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Nat Genet. 2016 Mar;48(3):245-52 26854917
Cites Exp Biol Med (Maywood). 2010 Jul;235(7):785-95 20558833
Cites N Engl J Med. 2015 Sep 3;373(10 ):895-907 26287746
Cites Nature. 2015 Feb 19;518(7539):317-30 25693563
Cites Int J Epidemiol. 2014 Apr;43(2):576-85 24671021
Cites Nat Neurosci. 2014 Oct;17 (10 ):1418-1428 25174004
Cites Cell. 2015 Aug 27;162(5):1051-65 26300125
Cites Am J Hum Genet. 2013 Nov 7;93(5):779-97 24210251
Cites Nat Genet. 2016 May;48(5):488-96 27064255
Cites Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1050-1057 28279971
Cites Nat Rev Genet. 2016 Aug 1;17 (9):551-65 27479905
Cites PLoS Genet. 2013;9(3):e1003355 23505390
Cites Nature. 2014 Jul 24;511(7510):421-7 25056061
Cites Stat Methods Med Res. 2017 Oct;26(5):2333-2355 26282889
Cites Nat Rev Genet. 2011 Jul 12;12(8):529-41 21747404
Cites Nucleic Acids Res. 2010 Jan;38(3):e17 19923232
Cites Nat Genet. 2013 Oct;45(10 ):1238-1243 24013639
Cites Aging (Albany NY). 2016 Sep 28;8(9):1844-1865 27690265
Cites Nat Neurosci. 2016 Nov;19(11):1442-1453 27668389
Cites Science. 2016 Apr 29;352(6285):600-4 27126046
Cites Nucleic Acids Res. 2014 Jan;42(Database issue):D1001-6 24316577
Cites Nat Genet. 2015 Sep;47(9):979-986 26192919
Cites PLoS Genet. 2014 May 15;10(5):e1004383 24830394
Cites Nature. 2017 Jan 5;541(7635):81-86 28002404
Cites Science. 2013 Mar 1;339(6123):1074-7 23328393
Cites Am J Hum Genet. 2011 Nov 11;89(5):607-18 22077970
Cites Am J Hum Genet. 2017 Feb 2;100(2):371 28157541
Cites Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41 21059682
Cites Nature. 2012 Sep 6;489(7414):57-74 22955616
Cites Nat Genet. 2015 Oct;47(10 ):1121-1130 26343387
Cites Cell. 2016 Jun 2;165(6):1519-1529 27259153
Cites Nat Genet. 2014 Nov;46(11):1173-86 25282103
Cites Genome Biol. 2004;5(10):R80 15461798
Cites Epigenetics Chromatin. 2013 Mar 03;6(1):4 23452981
Cites Nature. 2014 Feb 20;506(7488):376-81 24390342
Cites Genome Res. 2012 Sep;22(9):1760-74 22955987
Cites Genome Biol. 2017 May 16;18(1):86 28506277
Cites Nat Genet. 2015 Nov;47(11):1236-41 26414676
Cites Sci Rep. 2016 Sep 08;6:32894 27604177
Cites Nature. 2010 Aug 5;466(7307):714-9 20686566
Cites Nat Genet. 2016 May;48(5):481-7 27019110
Cites Nat Rev Genet. 2014 Apr;15(4):272-86 24614317
Cites Nature. 2016 May 11;533(7604):539-42 27225129
Cites Nat Genet. 2016 Jul;48(7):709-17 27182965
Cites Nat Genet. 2017 Jan;49(1):139-145 27918533
Cites Nat Genet. 2013 Dec;45(12):1452-8 24162737
Cites Lancet Diabetes Endocrinol. 2015 Jul;3(7):526-534 26095709
Cites Nature. 2014 Feb 27;506(7489):456-62 24553140
Cites Cell. 2017 Jun 15;169(7):1177-1186 28622505
Cites Stat Med. 2008 Apr 15;27(8):1133-63 17886233
Cites PLoS Med. 2015 Mar 31;12 (3):e1001779 25826379
Cites Nature. 2015 Feb 12;518(7538):187-196 25673412
Cites Nature. 2014 Mar 20;507(7492):371-5 24646999
Cites Nat Genet. 2015 Sep;47(9):1091-8 26258848
Cites Nature. 2010 Oct 28;467(7319):1061-73 20981092
Cites Nat Biotechnol. 2016 Feb;34(2):192-8 26751173
Cites Nat Genet. 2013 Nov;45(11):1274-1283 24097068
Cites Am J Hum Genet. 2012 Jan 13;90(1):7-24 22243964
Cites Am J Hum Genet. 2017 Jun 1;100(6):954-959 28528868
Cites Nat Methods. 2012 Feb 28;9(3):215-6 22373907
Cites Nature. 2015 Jan 15;517(7534):321-6 25592537
Cites PLoS One. 2012;7(4):e35430 22563384
Cites Nat Genet. 2012 Sep;44(9):981-90 22885922
Cites Nat Biotechnol. 2013 Feb;31(2):142-7 23334450
Cites Nature. 2015 Feb 19;518(7539):337-43 25363779
Cites Science. 2015 May 8;348(6235):648-60 25954001
Cites Nature. 2012 Oct 11;490(7419):267-72 22982992
Cites Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36 21948793
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007