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

Autor: Wu Y; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Zeng J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Zhang F; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Zhu Z; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Qi T; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Zheng Z; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.; The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China., Lloyd-Jones LR; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Marioni RE; Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.; Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK., Martin NG; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia., Montgomery GW; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Deary IJ; Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK., Wray NR; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia., Visscher PM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia., McRae AF; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Yang J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. jian.yang@uq.edu.au.; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia. jian.yang@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Mar 02; Vol. 9 (1), pp. 918. Date of Electronic Publication: 2018 Mar 02.
DOI: 10.1038/s41467-018-03371-0
Abstrakt: 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.
Databáze: MEDLINE