Contribution of genetic variation to transgenerational inheritance of DNA methylation
Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying ass...
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description | Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to intrauterine differences between monozygotic and dizygotic twins. We estimate the heritability of DNA methylation on peripheral blood leukocytes using Illumina HumanMethylation450 array using a family based sample of 614 people from 117 families, allowing comparison both within and across generations.
The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to genetic effects with any common environmental or zygotic effects being limited. The average heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes.
The majority of transgenerational similarity in DNA methylation is attributable to genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites. |
doi_str_mv | 10.1186/gb-2014-15-5-r73 |
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The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to genetic effects with any common environmental or zygotic effects being limited. The average heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes.
The majority of transgenerational similarity in DNA methylation is attributable to genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites.</description><identifier>ISSN: 1474-760X</identifier><identifier>ISSN: 1465-6906</identifier><identifier>EISSN: 1474-760X</identifier><identifier>EISSN: 1465-6914</identifier><identifier>DOI: 10.1186/gb-2014-15-5-r73</identifier><identifier>PMID: 24887635</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Analysis ; Chromosomes, Human ; DNA Methylation ; DNA sequencing ; European Continental Ancestry Group - genetics ; Genes ; Genetic aspects ; Genetic transcription ; Genetic Variation ; Humans ; Molecular Sequence Data ; Nucleotide sequencing ; Oligonucleotide Array Sequence Analysis - methods ; Pedigree ; Polymorphism, Single Nucleotide ; Twins, Dizygotic - genetics ; Twins, Monozygotic - genetics</subject><ispartof>Genome Biology (Online Edition), 2014-05, Vol.15 (5), p.R73-R73, Article R73</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>Copyright © 2014 McRae et al.; licensee BioMed Central Ltd. 2014 McRae et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b690t-39016d5108189e69d3eb936cd7166b7deccf523085db926b228b2a80b75d8d1a3</citedby><cites>FETCH-LOGICAL-b690t-39016d5108189e69d3eb936cd7166b7deccf523085db926b228b2a80b75d8d1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072933/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072933/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24887635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McRae, Allan F</creatorcontrib><creatorcontrib>Powell, Joseph E</creatorcontrib><creatorcontrib>Henders, Anjali K</creatorcontrib><creatorcontrib>Bowdler, Lisa</creatorcontrib><creatorcontrib>Hemani, Gibran</creatorcontrib><creatorcontrib>Shah, Sonia</creatorcontrib><creatorcontrib>Painter, Jodie N</creatorcontrib><creatorcontrib>Martin, Nicholas G</creatorcontrib><creatorcontrib>Visscher, Peter M</creatorcontrib><creatorcontrib>Montgomery, Grant W</creatorcontrib><title>Contribution of genetic variation to transgenerational inheritance of DNA methylation</title><title>Genome Biology (Online Edition)</title><addtitle>Genome Biol</addtitle><description>Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to intrauterine differences between monozygotic and dizygotic twins. We estimate the heritability of DNA methylation on peripheral blood leukocytes using Illumina HumanMethylation450 array using a family based sample of 614 people from 117 families, allowing comparison both within and across generations.
The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to genetic effects with any common environmental or zygotic effects being limited. The average heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes.
The majority of transgenerational similarity in DNA methylation is attributable to genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites.</description><subject>Adult</subject><subject>Analysis</subject><subject>Chromosomes, Human</subject><subject>DNA Methylation</subject><subject>DNA sequencing</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Genetic Variation</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Nucleotide sequencing</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Pedigree</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Twins, Dizygotic - genetics</subject><subject>Twins, Monozygotic - genetics</subject><issn>1474-760X</issn><issn>1465-6906</issn><issn>1474-760X</issn><issn>1465-6914</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>KPI</sourceid><recordid>eNqNkk1v1DAQhiMEoqVw54RyhEOKP-KPXJBWC4WKCjhQiZtlO5OsUWIX26nov693t1RdCSTkw1gzz_tqZjRV9RKjU4wlfzuahiDcNpg1rImCPqqOcSvaRnD04_GD_1H1LKWfCOGuJfxpdURaKQWn7Li6XAefozNLdsHXYahH8JCdra91dHqXzKHOUfu0rcRdSk-18xuILmtvYat6_2VVz5A3N9MOeF49GfSU4MVdPKkuzz58X39qLr5-PF-vLhrDO5Qb2iHMe4aRxLID3vUUTEe57QXm3IgerB0YoUiy3nSEG0KkIVoiI1gve6zpSfVu73u1mBl6C2UWPamr6GYdb1TQTh1WvNuoMVyrFgnSUVoM1nsD48I_DA4rNsxqNGq7dYWZYqpsvbi8vmsjhl8LpKxmlyxMk_YQllRAxjjuMOb_gbZCcsYlKejpHh31BMr5IZQObHk9zM4GD4Mr-RVrEZe0nEMRvDkQFCbD7zzqJSX1-dv5IYv2rI0hpQjD_cwYqe1t_W3KVw-XfS_4c0z0FmF9zIU</recordid><startdate>20140529</startdate><enddate>20140529</enddate><creator>McRae, Allan F</creator><creator>Powell, Joseph E</creator><creator>Henders, Anjali K</creator><creator>Bowdler, Lisa</creator><creator>Hemani, Gibran</creator><creator>Shah, Sonia</creator><creator>Painter, Jodie N</creator><creator>Martin, Nicholas G</creator><creator>Visscher, Peter M</creator><creator>Montgomery, Grant W</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>KPI</scope><scope>IAO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140529</creationdate><title>Contribution of genetic variation to transgenerational inheritance of DNA methylation</title><author>McRae, Allan F ; Powell, Joseph E ; Henders, Anjali K ; Bowdler, Lisa ; Hemani, Gibran ; Shah, Sonia ; Painter, Jodie N ; Martin, Nicholas G ; Visscher, Peter M ; Montgomery, Grant W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b690t-39016d5108189e69d3eb936cd7166b7deccf523085db926b228b2a80b75d8d1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Analysis</topic><topic>Chromosomes, Human</topic><topic>DNA Methylation</topic><topic>DNA sequencing</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>Nucleotide sequencing</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Pedigree</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Twins, Dizygotic - genetics</topic><topic>Twins, Monozygotic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McRae, Allan F</creatorcontrib><creatorcontrib>Powell, Joseph E</creatorcontrib><creatorcontrib>Henders, Anjali K</creatorcontrib><creatorcontrib>Bowdler, Lisa</creatorcontrib><creatorcontrib>Hemani, Gibran</creatorcontrib><creatorcontrib>Shah, Sonia</creatorcontrib><creatorcontrib>Painter, Jodie N</creatorcontrib><creatorcontrib>Martin, Nicholas G</creatorcontrib><creatorcontrib>Visscher, Peter M</creatorcontrib><creatorcontrib>Montgomery, Grant W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Global Issues</collection><collection>Gale Academic OneFile</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome Biology (Online Edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McRae, Allan F</au><au>Powell, Joseph E</au><au>Henders, Anjali K</au><au>Bowdler, Lisa</au><au>Hemani, Gibran</au><au>Shah, Sonia</au><au>Painter, Jodie N</au><au>Martin, Nicholas G</au><au>Visscher, Peter M</au><au>Montgomery, Grant W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contribution of genetic variation to transgenerational inheritance of DNA methylation</atitle><jtitle>Genome Biology (Online Edition)</jtitle><addtitle>Genome Biol</addtitle><date>2014-05-29</date><risdate>2014</risdate><volume>15</volume><issue>5</issue><spage>R73</spage><epage>R73</epage><pages>R73-R73</pages><artnum>R73</artnum><issn>1474-760X</issn><issn>1465-6906</issn><eissn>1474-760X</eissn><eissn>1465-6914</eissn><abstract>Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to intrauterine differences between monozygotic and dizygotic twins. We estimate the heritability of DNA methylation on peripheral blood leukocytes using Illumina HumanMethylation450 array using a family based sample of 614 people from 117 families, allowing comparison both within and across generations.
The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to genetic effects with any common environmental or zygotic effects being limited. The average heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes.
The majority of transgenerational similarity in DNA methylation is attributable to genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24887635</pmid><doi>10.1186/gb-2014-15-5-r73</doi><oa>free_for_read</oa></addata></record> |
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subjects | Adult Analysis Chromosomes, Human DNA Methylation DNA sequencing European Continental Ancestry Group - genetics Genes Genetic aspects Genetic transcription Genetic Variation Humans Molecular Sequence Data Nucleotide sequencing Oligonucleotide Array Sequence Analysis - methods Pedigree Polymorphism, Single Nucleotide Twins, Dizygotic - genetics Twins, Monozygotic - genetics |
title | Contribution of genetic variation to transgenerational inheritance of DNA methylation |
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