Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci

Mathieu Lemire; Syed H.E. Zaidi; Maria Ban; Bing Ge; Dylan Aïssi; Marine Germain; Irfahan Kassam; Mike Wang; Brent W. Zanke; France Gagnon; Pierre Emmanuel Morange; David Alexandre Trégouët; Philip S. Wells; Stephen Sawcer; Steven Gallinger; Tomi Pastinen; Thomas J. Hudson

doi:10.1038/ncomms7326

Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci

Mathieu Lemire, Syed H.E. Zaidi, Maria Ban, Bing Ge, Dylan Aïssi, Marine Germain, Irfahan Kassam, Mike Wang, Brent W. Zanke, France Gagnon, Pierre Emmanuel Morange, David Alexandre Trégouët, Philip S. Wells, Stephen Sawcer, Steven Gallinger, Tomi Pastinen, Thomas J. Hudson

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100 Scopus citations

Abstract

The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P<3.2 × 10 â '13; FDR<5%). These trans-meQTLs include 1,657 SNP-CpG pairs from different chromosomes and 262 pairs from the same chromosome that are >1‰Mb apart. Over 90% of these pairs are replicated (FDR<5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (P<0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states.

Original language	English
Article number	6326
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7326
State	Published - 25 Feb 2015
Externally published	Yes

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Lemire, M., Zaidi, S. H. E., Ban, M., Ge, B., Aïssi, D., Germain, M., Kassam, I., Wang, M., Zanke, B. W., Gagnon, F., Morange, P. E., Trégouët, D. A., Wells, P. S., Sawcer, S., Gallinger, S., Pastinen, T., & Hudson, T. J. (2015). Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci. Nature Communications, 6, Article 6326. https://doi.org/10.1038/ncomms7326

@article{e1bedb59b30543118f754725793f25cd,

title = "Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci",

abstract = "The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P<3.2 × 10 {\^a} '13; FDR<5%). These trans-meQTLs include 1,657 SNP-CpG pairs from different chromosomes and 262 pairs from the same chromosome that are >1‰Mb apart. Over 90% of these pairs are replicated (FDR<5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (P<0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states.",

author = "Mathieu Lemire and Zaidi, {Syed H.E.} and Maria Ban and Bing Ge and Dylan A{\"i}ssi and Marine Germain and Irfahan Kassam and Mike Wang and Zanke, {Brent W.} and France Gagnon and Morange, {Pierre Emmanuel} and Tr{\'e}gou{\"e}t, {David Alexandre} and Wells, {Philip S.} and Stephen Sawcer and Steven Gallinger and Tomi Pastinen and Hudson, {Thomas J.}",

year = "2015",

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day = "25",

doi = "10.1038/ncomms7326",

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journal = "Nature Communications",

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Lemire, M, Zaidi, SHE, Ban, M, Ge, B, Aïssi, D, Germain, M, Kassam, I, Wang, M, Zanke, BW, Gagnon, F, Morange, PE, Trégouët, DA, Wells, PS, Sawcer, S, Gallinger, S, Pastinen, T & Hudson, TJ 2015, 'Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci', Nature Communications, vol. 6, 6326. https://doi.org/10.1038/ncomms7326

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T1 - Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci

AU - Lemire, Mathieu

AU - Zaidi, Syed H.E.

AU - Ban, Maria

AU - Ge, Bing

AU - Aïssi, Dylan

AU - Germain, Marine

AU - Kassam, Irfahan

AU - Wang, Mike

AU - Zanke, Brent W.

AU - Gagnon, France

AU - Morange, Pierre Emmanuel

AU - Trégouët, David Alexandre

AU - Wells, Philip S.

AU - Sawcer, Stephen

AU - Gallinger, Steven

AU - Pastinen, Tomi

AU - Hudson, Thomas J.

PY - 2015/2/25

Y1 - 2015/2/25

N2 - The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P<3.2 × 10 â '13; FDR<5%). These trans-meQTLs include 1,657 SNP-CpG pairs from different chromosomes and 262 pairs from the same chromosome that are >1‰Mb apart. Over 90% of these pairs are replicated (FDR<5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (P<0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states.

AB - The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P<3.2 × 10 â '13; FDR<5%). These trans-meQTLs include 1,657 SNP-CpG pairs from different chromosomes and 262 pairs from the same chromosome that are >1‰Mb apart. Over 90% of these pairs are replicated (FDR<5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (P<0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states.

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SN - 2041-1723

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JO - Nature Communications

JF - Nature Communications

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Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci

Abstract

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