Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits
| Autor: | Peter M. Visscher, Jian Zeng, Ting Qi, Riccardo E. Marioni, Nicholas G. Martin, Zhili Zheng, Allan F. McRae, Futao Zhang, Yang Wu, Grant W. Montgomery, Jian Yang, Ian J. Deary, Naomi R. Wray, Zhihong Zhu, Luke R. Lloyd-Jones |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Science Quantitative Trait Loci General Physics and Astronomy Genomics Genome-wide association study Computational biology Regulatory Sequences Nucleic Acid Quantitative trait locus Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Quantitative Trait Heritable Humans genetics Genetic Predisposition to Disease RNA Messenger lcsh:Science data integration Gene Epigenomics Multidisciplinary dNaM General Chemistry DNA Methylation Phenotype 030104 developmental biology Organ Specificity epigenomics DNA methylation Schizophrenia lcsh:Q Transcriptome Genome-Wide Association Study |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) Nature Communications Wu, Y, Zeng, J, Zhang, F, Zhu, Z, Qi, T, Zheng, Z, Luke R, L-J, Marioni, R, Martin, N G, Montgomery, G W, Deary, I J, Visscher, P, Mcrae, A F & Yang, J 2018, ' Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits ', Nature Communications, vol. 9, 918, pp. 1-14 . https://doi.org/10.1038/s41467-018-03371-0 |
| ISSN: | 2041-1723 |
| Popis: | 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. The identification of the causal gene at a GWAS locus remains to be a challenging task. Here, using the SMR & HEIDI method to integrate GWAS, eQTL and mQTL data, Wu et al. map DNA methylation sites to the transcriptome and thereby prioritize functionally relevant genes for 12 human complex traits. |
| Databáze: | OpenAIRE |
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