Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits

Wu, Yang, Zeng, Jian, Zhang, Futao, Zhu, Zhihong, Qi, Ting, Zheng, Zhili, Lloyd-Jones, Luke R., Marioni, Riccardo E., Martin, Nicholas G., Montgomery, Grant W., Deary, Ian J., Wray, Naomi R., Visscher, Peter M., McRae, Allan F. and Yang, Jian (2018) Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits. Nature Communications, 9 918: . doi:10.1038/s41467-018-03371-0


Author Wu, Yang
Zeng, Jian
Zhang, Futao
Zhu, Zhihong
Qi, Ting
Zheng, Zhili
Lloyd-Jones, Luke R.
Marioni, Riccardo E.
Martin, Nicholas G.
Montgomery, Grant W.
Deary, Ian J.
Wray, Naomi R.
Visscher, Peter M.
McRae, Allan F.
Yang, Jian
Title Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2018-03-02
Year available 2018
Sub-type Article (original research)
DOI 10.1038/s41467-018-03371-0
Open Access Status DOI
Volume 9
Issue 918
Total pages 14
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
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.
Keyword Epigenome-Wide Association
Coronary-Artery-Disease
Body-Mass Index
Dna Methylation
Human Genome
Susceptibility Loci
Genetic-Variation
Variants
Risk
Gwas
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP160101343
1107258
R01 MH100141
MR/K026992/1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Institute for Molecular Bioscience - Publications
 
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Created: Wed, 07 Mar 2018, 11:02:23 EST