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Contribution of genetic variation to transgenerational inheritance of DNA methylation
BACKGROUND: 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 un...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072933/ https://www.ncbi.nlm.nih.gov/pubmed/24887635 http://dx.doi.org/10.1186/gb-2014-15-5-r73 |
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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_facet | 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 | McRae, Allan F |
collection | PubMed |
description | BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-4072933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40729332014-07-01 Contribution of genetic variation to transgenerational inheritance of DNA methylation 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 Genome Biol Research BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2014 2014-05-29 /pmc/articles/PMC4072933/ /pubmed/24887635 http://dx.doi.org/10.1186/gb-2014-15-5-r73 Text en Copyright © 2014 McRae et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research 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 Contribution of genetic variation to transgenerational inheritance of DNA methylation |
title | Contribution of genetic variation to transgenerational inheritance of DNA methylation |
title_full | Contribution of genetic variation to transgenerational inheritance of DNA methylation |
title_fullStr | Contribution of genetic variation to transgenerational inheritance of DNA methylation |
title_full_unstemmed | Contribution of genetic variation to transgenerational inheritance of DNA methylation |
title_short | Contribution of genetic variation to transgenerational inheritance of DNA methylation |
title_sort | contribution of genetic variation to transgenerational inheritance of dna methylation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072933/ https://www.ncbi.nlm.nih.gov/pubmed/24887635 http://dx.doi.org/10.1186/gb-2014-15-5-r73 |
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