Identification of 55,000 Replicated DNA Methylation QTL

Allan F McRae; Riccardo E Marioni; Sonia Shah; Jian Yang; Joseph E Powell; Sarah E Harris; Jude Gibson; Anjali K Henders; Lisa Bowdler; Jodie N Painter; Lee Murphy; Nicholas G Martin; John M Starr; Naomi R Wray; Ian J Deary; Peter M Visscher; Grant W Montgomery

doi:10.1038/s41598-018-35871-w

Identification of 55,000 Replicated DNA Methylation QTL

Allan F McRae, Riccardo E Marioni, Sonia Shah, Jian Yang, Joseph E Powell, Sarah E Harris, Jude Gibson, Anjali K Henders, Lisa Bowdler, Jodie N Painter, Lee Murphy, Nicholas G Martin, John M Starr, Naomi R Wray, Ian J Deary, Peter M Visscher, Grant W Montgomery

Research output: Contribution to journal › Article › peer-review

Abstract

DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood 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 1 Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5' UTR regions. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1 × 10-10), ulcerative colitis (p = 2 × 10-5), Crohn's disease (p = 6 × 10-8) and coronary artery disease (p = 5.5 × 10-6) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs.

Original language	English
Article number	17605
Pages (from-to)	1-9
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-35871-w
Publication status	Published - 4 Dec 2018

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3 Finished

The Disconnected Mind Phase 3
Wardlaw, J.
UK-based charities
1/04/16 → 30/09/20
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, R., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
Project: Research
A genome wide association study of non pathological cognitive ageing
Deary, I., Porteous, D. & Tenesa, A.
BBSRC
1/09/08 → 31/08/10
Project: Research

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McRae, A. F., Marioni, R. E., Shah, S., Yang, J., Powell, J. E., Harris, S. E., Gibson, J., Henders, A. K., Bowdler, L., Painter, J. N., Murphy, L., Martin, N. G., Starr, J. M., Wray, N. R., Deary, I. J., Visscher, P. M., & Montgomery, G. W. (2018). Identification of 55,000 Replicated DNA Methylation QTL. Scientific Reports, 8(1), 1-9. [17605]. https://doi.org/10.1038/s41598-018-35871-w

McRae, Allan F ; Marioni, Riccardo E ; Shah, Sonia ; Yang, Jian ; Powell, Joseph E ; Harris, Sarah E ; Gibson, Jude ; Henders, Anjali K ; Bowdler, Lisa ; Painter, Jodie N ; Murphy, Lee ; Martin, Nicholas G ; Starr, John M ; Wray, Naomi R ; Deary, Ian J ; Visscher, Peter M ; Montgomery, Grant W. / Identification of 55,000 Replicated DNA Methylation QTL. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 1-9.

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abstract = "DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood 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 1 Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5' UTR regions. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1 × 10-10), ulcerative colitis (p = 2 × 10-5), Crohn's disease (p = 6 × 10-8) and coronary artery disease (p = 5.5 × 10-6) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs.",

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Identification of 55,000 Replicated DNA Methylation QTL. / McRae, Allan F; Marioni, Riccardo E; Shah, Sonia; Yang, Jian; Powell, Joseph E; Harris, Sarah E; Gibson, Jude; Henders, Anjali K; Bowdler, Lisa; Painter, Jodie N; Murphy, Lee; Martin, Nicholas G; Starr, John M; Wray, Naomi R; Deary, Ian J; Visscher, Peter M; Montgomery, Grant W.

In: Scientific Reports, Vol. 8, No. 1, 17605, 04.12.2018, p. 1-9.

Research output: Contribution to journal › Article › peer-review

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AU - Marioni, Riccardo E

AU - Shah, Sonia

AU - Yang, Jian

AU - Powell, Joseph E

AU - Harris, Sarah E

AU - Gibson, Jude

AU - Henders, Anjali K

AU - Bowdler, Lisa

AU - Painter, Jodie N

AU - Murphy, Lee

AU - Martin, Nicholas G

AU - Starr, John M

AU - Wray, Naomi R

AU - Deary, Ian J

AU - Visscher, Peter M

AU - Montgomery, Grant W

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N2 - DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood 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 1 Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5' UTR regions. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1 × 10-10), ulcerative colitis (p = 2 × 10-5), Crohn's disease (p = 6 × 10-8) and coronary artery disease (p = 5.5 × 10-6) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs.

AB - DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood 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 1 Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5' UTR regions. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1 × 10-10), ulcerative colitis (p = 2 × 10-5), Crohn's disease (p = 6 × 10-8) and coronary artery disease (p = 5.5 × 10-6) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs.

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DO - 10.1038/s41598-018-35871-w

M3 - Article

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VL - 8

SP - 1

EP - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 17605

ER -

Identification of 55,000 Replicated DNA Methylation QTL

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The Disconnected Mind Phase 3

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A genome wide association study of non pathological cognitive ageing

Cite this