VTRNA2-1 : Genetic Variation, Heritable Methylation and Disease Association
is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DN...
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| Veröffentlicht in: | International journal of molecular sciences 2021-03, Vol.22 (5), p.2535 |
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| creator | Dugué, Pierre-Antoine Yu, Chenglong McKay, Timothy Wong, Ee Ming Joo, Jihoon Eric Tsimiklis, Helen Hammet, Fleur Mahmoodi, Maryam Theys, Derrick kConFab Hopper, John L Giles, Graham G Milne, Roger L Steen, Jason A Dowty, James G Nguyen-Dumont, Tu Southey, Melissa C |
| description | is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the
gene region in multiple-case breast cancer families in which
methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The
-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with
methylation (
< 1.5 × 10
); however, these explained little of the methylation variation (R
< 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence
methylation. SNP-based heritability estimates were consistent with the mQTL findings (h
= 0, 95%CI: -0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at
. Genetic factors and adult lifestyle play a minimal role in explaining methylation variability at the heritable
cluster. |
| doi_str_mv | 10.3390/ijms22052535 |
| format | Article |
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gene region in multiple-case breast cancer families in which
methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The
-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with
methylation (
< 1.5 × 10
); however, these explained little of the methylation variation (R
< 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence
methylation. SNP-based heritability estimates were consistent with the mQTL findings (h
= 0, 95%CI: -0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at
. Genetic factors and adult lifestyle play a minimal role in explaining methylation variability at the heritable
cluster.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22052535</identifier><identifier>PMID: 33802562</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Aged ; Blood ; Body mass index ; Body size ; Breast cancer ; Breast Neoplasms - genetics ; Case-Control Studies ; Collaboration ; CpG islands ; CpG Islands - genetics ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; Female ; Genetic diversity ; Genetic factors ; Genome-Wide Association Study - methods ; Genomes ; Genotyping ; Heritability ; Humans ; Influence ; Kinases ; Male ; MicroRNAs - genetics ; Middle Aged ; Nucleotide sequence ; Phosphorylation ; Polymorphism, Single Nucleotide - genetics ; Prospective Studies ; Prostate cancer ; Quantitative trait loci ; Quantitative Trait Loci - genetics ; Single-nucleotide polymorphism</subject><ispartof>International journal of molecular sciences, 2021-03, Vol.22 (5), p.2535</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-7879f695c0c5f14b9c95cba31f12cd0e030cd28060f4272fb8a418c0db01b9123</citedby><cites>FETCH-LOGICAL-c412t-7879f695c0c5f14b9c95cba31f12cd0e030cd28060f4272fb8a418c0db01b9123</cites><orcidid>0000-0002-6313-9005</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/PMC7961504/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961504/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33802562$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dugué, Pierre-Antoine</creatorcontrib><creatorcontrib>Yu, Chenglong</creatorcontrib><creatorcontrib>McKay, Timothy</creatorcontrib><creatorcontrib>Wong, Ee Ming</creatorcontrib><creatorcontrib>Joo, Jihoon Eric</creatorcontrib><creatorcontrib>Tsimiklis, Helen</creatorcontrib><creatorcontrib>Hammet, Fleur</creatorcontrib><creatorcontrib>Mahmoodi, Maryam</creatorcontrib><creatorcontrib>Theys, Derrick</creatorcontrib><creatorcontrib>kConFab</creatorcontrib><creatorcontrib>Hopper, John L</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Steen, Jason A</creatorcontrib><creatorcontrib>Dowty, James G</creatorcontrib><creatorcontrib>Nguyen-Dumont, Tu</creatorcontrib><creatorcontrib>Southey, Melissa C</creatorcontrib><title>VTRNA2-1 : Genetic Variation, Heritable Methylation and Disease Association</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the
gene region in multiple-case breast cancer families in which
methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The
-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with
methylation (
< 1.5 × 10
); however, these explained little of the methylation variation (R
< 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence
methylation. SNP-based heritability estimates were consistent with the mQTL findings (h
= 0, 95%CI: -0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at
. Genetic factors and adult lifestyle play a minimal role in explaining methylation variability at the heritable
cluster.</description><subject>Aged</subject><subject>Blood</subject><subject>Body mass index</subject><subject>Body size</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Case-Control Studies</subject><subject>Collaboration</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Female</subject><subject>Genetic diversity</subject><subject>Genetic factors</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Heritability</subject><subject>Humans</subject><subject>Influence</subject><subject>Kinases</subject><subject>Male</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Nucleotide sequence</subject><subject>Phosphorylation</subject><subject>Polymorphism, Single Nucleotide - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dugué, Pierre-Antoine</au><au>Yu, Chenglong</au><au>McKay, Timothy</au><au>Wong, Ee Ming</au><au>Joo, Jihoon Eric</au><au>Tsimiklis, Helen</au><au>Hammet, Fleur</au><au>Mahmoodi, Maryam</au><au>Theys, Derrick</au><au>kConFab</au><au>Hopper, John L</au><au>Giles, Graham G</au><au>Milne, Roger L</au><au>Steen, Jason A</au><au>Dowty, James G</au><au>Nguyen-Dumont, Tu</au><au>Southey, Melissa C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>VTRNA2-1 : Genetic Variation, Heritable Methylation and Disease Association</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2021-03-03</date><risdate>2021</risdate><volume>22</volume><issue>5</issue><spage>2535</spage><pages>2535-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the
gene region in multiple-case breast cancer families in which
methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The
-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with
methylation (
< 1.5 × 10
); however, these explained little of the methylation variation (R
< 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence
methylation. SNP-based heritability estimates were consistent with the mQTL findings (h
= 0, 95%CI: -0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at
. Genetic factors and adult lifestyle play a minimal role in explaining methylation variability at the heritable
cluster.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33802562</pmid><doi>10.3390/ijms22052535</doi><orcidid>https://orcid.org/0000-0002-6313-9005</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Aged Blood Body mass index Body size Breast cancer Breast Neoplasms - genetics Case-Control Studies Collaboration CpG islands CpG Islands - genetics Deoxyribonucleic acid DNA DNA methylation DNA Methylation - genetics Female Genetic diversity Genetic factors Genome-Wide Association Study - methods Genomes Genotyping Heritability Humans Influence Kinases Male MicroRNAs - genetics Middle Aged Nucleotide sequence Phosphorylation Polymorphism, Single Nucleotide - genetics Prospective Studies Prostate cancer Quantitative trait loci Quantitative Trait Loci - genetics Single-nucleotide polymorphism |
| title | VTRNA2-1 : Genetic Variation, Heritable Methylation and Disease Association |
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