Identification of 55,000 Replicated DNA Methylation QTL
Allan F. McRae,
Riccardo E Marioni,
Joseph E. Powell,
Sarah E. Harris,
Anjali K Henders,
Jodie N Painter,
Nicholas G Martin,
John M. Starr,
Naomi R. Wray,
Ian J Deary,
Peter M Visscher,
Grant W. Montgomery
Posted 21 Jul 2017
bioRxiv DOI: 10.1101/166710 (published DOI: 10.1038/s41598-018-35871-w)
Posted 21 Jul 2017
DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is thus a potential candidate for explaining the many identified SNP associations with diseases and complex traits that are not found in coding regions. We identified and replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation measured on Illumina HumanMethylation450 arrays in the Brisbane Systems Genetics Study (n=614 from 177 families) and the Lothian Birth Cohorts of 1921 and 1936 (combined n = 1366). The trans mQTL SNPs were found to be over-represented in the subtelomeric 1Mbp of the genome and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5' UTR regions. No association was observed between either the SNPs or DNA methylation sites of trans mQTL and telomere length. LD Score regression was used to partition the heritability for a number of complex traits and diseases into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1x10^-10), ulcerative colitis (p = 2x10^-5), Crohn's disease (p = 6x10^-8) and coronary artery disease (p = 5.5x10^-6) when compared to a random sample of SNPs with matched minor allele frequency. This enrichment is explained by the genomic location of the mQTL SNPs, which are biased towards genic regions of the genome due to the combination of the vast majority being located in cis to the DNA methylation probes and the probes on the array being over-representing genic regions.
- Downloaded 1,013 times
- Download rankings, all-time:
- Site-wide: 16,727 out of 118,387
- In genomics: 1,814 out of 6,435
- Year to date:
- Site-wide: 73,671 out of 118,387
- Since beginning of last month:
- Site-wide: 65,051 out of 118,387
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!