Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci
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 l...
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| Veröffentlicht in: | Nature communications 2015-02, Vol.6 (1), p.6326-6326, Article 6326 |
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| creator | Lemire, Mathieu Zaidi, Syed H.E. Ban, Maria Ge, Bing Aïssi, Dylan Germain, Marine Kassam, Irfahan Wang, Mike Zanke, Brent W. Gagnon, France Morange, Pierre-Emmanuel Trégouët, David-Alexandre Wells, Philip S. Sawcer, Stephen Gallinger, Steven Pastinen, Tomi Hudson, Thomas J. |
| description | 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 |
| doi_str_mv | 10.1038/ncomms7326 |
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trans
) single-nucleotide polymorphism (SNP) (
P
<3.2 × 10
−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.
There is a functional link between SNPs and epigenetic variations when they are in close range, but the long-range effect is unclear. Here, by analysing methylation quantitative trait loci, the authors demonstrate that methylation levels at CpG sites in lymphocytes are correlated with distal SNPs.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms7326</identifier><identifier>PMID: 25716334</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/43 ; 38/61 ; 631/208/726/649 ; 631/208/729/743 ; 631/337/176 ; 631/67/1504/1885/1393 ; Autoimmune Diseases - genetics ; Biochemistry, Molecular Biology ; Case-Control Studies ; Colonic Neoplasms - genetics ; Colorectal cancer ; CpG Islands ; Datasets ; Disease ; DNA Methylation ; Epigenesis, Genetic ; Epigenetics ; Gene loci ; Genetics ; Genomes ; Genomics ; Genotype ; Hospitals ; Human genetics ; Humanities and Social Sciences ; Humans ; Life Sciences ; Lymphocytes ; Medical research ; Molecular biology ; multidisciplinary ; Nutrition ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Science ; Science (multidisciplinary) ; Thrombosis</subject><ispartof>Nature communications, 2015-02, Vol.6 (1), p.6326-6326, Article 6326</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Feb 2015</rights><rights>Attribution</rights><rights>Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c542t-7b68320b45a588d3f73702f8afa5afb5c78b343fa4aacf11edfb553eb7831d5c3</citedby><cites>FETCH-LOGICAL-c542t-7b68320b45a588d3f73702f8afa5afb5c78b343fa4aacf11edfb553eb7831d5c3</cites><orcidid>0000-0001-7685-0974 ; 0000-0002-1376-4849 ; 0000000213764849 ; 0000000176850974</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351585/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351585/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25716334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-01121790$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Lemire, Mathieu</creatorcontrib><creatorcontrib>Zaidi, Syed H.E.</creatorcontrib><creatorcontrib>Ban, Maria</creatorcontrib><creatorcontrib>Ge, Bing</creatorcontrib><creatorcontrib>Aïssi, Dylan</creatorcontrib><creatorcontrib>Germain, Marine</creatorcontrib><creatorcontrib>Kassam, Irfahan</creatorcontrib><creatorcontrib>Wang, Mike</creatorcontrib><creatorcontrib>Zanke, Brent W.</creatorcontrib><creatorcontrib>Gagnon, France</creatorcontrib><creatorcontrib>Morange, Pierre-Emmanuel</creatorcontrib><creatorcontrib>Trégouët, David-Alexandre</creatorcontrib><creatorcontrib>Wells, Philip S.</creatorcontrib><creatorcontrib>Sawcer, Stephen</creatorcontrib><creatorcontrib>Gallinger, Steven</creatorcontrib><creatorcontrib>Pastinen, Tomi</creatorcontrib><creatorcontrib>Hudson, Thomas J.</creatorcontrib><title>Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>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
−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.
There is a functional link between SNPs and epigenetic variations when they are in close range, but the long-range effect is unclear. Here, by analysing methylation quantitative trait loci, the authors demonstrate that methylation levels at CpG sites in lymphocytes are correlated with distal SNPs.</description><subject>38/43</subject><subject>38/61</subject><subject>631/208/726/649</subject><subject>631/208/729/743</subject><subject>631/337/176</subject><subject>631/67/1504/1885/1393</subject><subject>Autoimmune Diseases - genetics</subject><subject>Biochemistry, Molecular Biology</subject><subject>Case-Control Studies</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colorectal cancer</subject><subject>CpG Islands</subject><subject>Datasets</subject><subject>Disease</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Gene loci</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Hospitals</subject><subject>Human genetics</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Lymphocytes</subject><subject>Medical research</subject><subject>Molecular biology</subject><subject>multidisciplinary</subject><subject>Nutrition</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Quantitative Trait Loci</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Thrombosis</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkUFvFSEQx4nR2Kb24gcwJF60ZhUWWHgXk6ax1uQlXvRMZlnYR92FJ-y-pN9eNtvWZ-UAZOY3_4H5I_Sako-UMPUpmDiOWbK6eYZOa8JpRWXNnh_dT9B5zrekLLahivOX6KQWkjaM8VP0axtDXyUIvcV273sb7OQNTrafB5h8DNhnbGJwNiXb4fYOPyAHSH4lhmhgKkmY8LSLc4bQZRwd9qGze1u2MC2Mf4VeOBiyPb8_z9DP6y8_rm6q7fev364ut5URvJ4q2TaK1aTlAoRSHXOSSVI7BQ4EuFYYqVrGmQMOYByltitBwWwrFaOdMOwMfV5193M72s6U_gkGvU9-hHSnI3j9byb4ne7jQXMmqFCiCLxfBXZPym4ut3qJEUprKjfkQAv77r5Zir9nmyc9-mzsMECwZRaaNmIjG1kMKujbJ-htnFMoo1goxSmrxUJdrJRJMedk3eMLKNGL5fqv5QV-c_zVR_TB4AJ8WIFcUsXkdNTzf7k_ypO4aw</recordid><startdate>20150226</startdate><enddate>20150226</enddate><creator>Lemire, Mathieu</creator><creator>Zaidi, Syed H.E.</creator><creator>Ban, Maria</creator><creator>Ge, Bing</creator><creator>Aïssi, Dylan</creator><creator>Germain, Marine</creator><creator>Kassam, Irfahan</creator><creator>Wang, Mike</creator><creator>Zanke, Brent W.</creator><creator>Gagnon, France</creator><creator>Morange, Pierre-Emmanuel</creator><creator>Trégouët, David-Alexandre</creator><creator>Wells, Philip S.</creator><creator>Sawcer, Stephen</creator><creator>Gallinger, Steven</creator><creator>Pastinen, Tomi</creator><creator>Hudson, Thomas J.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Pub. 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epigenetic regulation is conferred by genetic variation located at thousands of independent loci</title><author>Lemire, Mathieu ; Zaidi, Syed H.E. ; Ban, Maria ; Ge, Bing ; Aïssi, Dylan ; Germain, Marine ; Kassam, Irfahan ; Wang, Mike ; Zanke, Brent W. ; Gagnon, France ; Morange, Pierre-Emmanuel ; Trégouët, David-Alexandre ; Wells, Philip S. ; Sawcer, Stephen ; Gallinger, Steven ; Pastinen, Tomi ; Hudson, Thomas J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c542t-7b68320b45a588d3f73702f8afa5afb5c78b343fa4aacf11edfb553eb7831d5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>38/43</topic><topic>38/61</topic><topic>631/208/726/649</topic><topic>631/208/729/743</topic><topic>631/337/176</topic><topic>631/67/1504/1885/1393</topic><topic>Autoimmune Diseases - genetics</topic><topic>Biochemistry, Molecular Biology</topic><topic>Case-Control Studies</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colorectal cancer</topic><topic>CpG Islands</topic><topic>Datasets</topic><topic>Disease</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Gene loci</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype</topic><topic>Hospitals</topic><topic>Human genetics</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Lymphocytes</topic><topic>Medical research</topic><topic>Molecular biology</topic><topic>multidisciplinary</topic><topic>Nutrition</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Quantitative Trait Loci</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Thrombosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lemire, Mathieu</creatorcontrib><creatorcontrib>Zaidi, Syed H.E.</creatorcontrib><creatorcontrib>Ban, 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Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lemire, Mathieu</au><au>Zaidi, Syed H.E.</au><au>Ban, Maria</au><au>Ge, Bing</au><au>Aïssi, Dylan</au><au>Germain, Marine</au><au>Kassam, Irfahan</au><au>Wang, Mike</au><au>Zanke, Brent W.</au><au>Gagnon, France</au><au>Morange, Pierre-Emmanuel</au><au>Trégouët, David-Alexandre</au><au>Wells, Philip S.</au><au>Sawcer, Stephen</au><au>Gallinger, Steven</au><au>Pastinen, Tomi</au><au>Hudson, Thomas J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2015-02-26</date><risdate>2015</risdate><volume>6</volume><issue>1</issue><spage>6326</spage><epage>6326</epage><pages>6326-6326</pages><artnum>6326</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><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
−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.
There is a functional link between SNPs and epigenetic variations when they are in close range, but the long-range effect is unclear. Here, by analysing methylation quantitative trait loci, the authors demonstrate that methylation levels at CpG sites in lymphocytes are correlated with distal SNPs.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25716334</pmid><doi>10.1038/ncomms7326</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-7685-0974</orcidid><orcidid>https://orcid.org/0000-0002-1376-4849</orcidid><orcidid>https://orcid.org/0000000213764849</orcidid><orcidid>https://orcid.org/0000000176850974</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-1723 |
| ispartof | Nature communications, 2015-02, Vol.6 (1), p.6326-6326, Article 6326 |
| issn | 2041-1723 2041-1723 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4351585 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA Free Journals |
| subjects | 38/43 38/61 631/208/726/649 631/208/729/743 631/337/176 631/67/1504/1885/1393 Autoimmune Diseases - genetics Biochemistry, Molecular Biology Case-Control Studies Colonic Neoplasms - genetics Colorectal cancer CpG Islands Datasets Disease DNA Methylation Epigenesis, Genetic Epigenetics Gene loci Genetics Genomes Genomics Genotype Hospitals Human genetics Humanities and Social Sciences Humans Life Sciences Lymphocytes Medical research Molecular biology multidisciplinary Nutrition Polymorphism, Single Nucleotide Quantitative Trait Loci Science Science (multidisciplinary) Thrombosis |
| title | Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T20%3A12%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Long-range%20epigenetic%20regulation%20is%20conferred%20by%20genetic%20variation%20located%20at%20thousands%20of%20independent%20loci&rft.jtitle=Nature%20communications&rft.au=Lemire,%20Mathieu&rft.date=2015-02-26&rft.volume=6&rft.issue=1&rft.spage=6326&rft.epage=6326&rft.pages=6326-6326&rft.artnum=6326&rft.issn=2041-1723&rft.eissn=2041-1723&rft_id=info:doi/10.1038/ncomms7326&rft_dat=%3Cproquest_pubme%3E1659767732%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1658413252&rft_id=info:pmid/25716334&rfr_iscdi=true |