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
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
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