Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data
DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore...
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| creator | Verschuren, Jeffrey J W Trompet, Stella Deelen, Joris Stott, David J Sattar, Naveed Buckley, Brendan M Ford, Ian Heijmans, Bastiaan T Guchelaar, Henk-Jan Houwing-Duistermaat, Jeanine J Slagboom, P Eline Jukema, J Wouter |
| description | DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.
The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.
The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.
This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts. |
| doi_str_mv | 10.1371/journal.pone.0056262 |
| format | Article |
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The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.
The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.
This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0056262</identifier><identifier>PMID: 23457540</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Analysis ; Apoptosis ; Base excision repair ; Biology ; Cardiovascular disease ; Cardiovascular diseases ; Cell death ; Chromosome Mapping ; Damage accumulation ; Defects ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA damage ; DNA Damage - genetics ; DNA End-Joining Repair - genetics ; DNA repair ; Female ; Genes ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genetic research ; Genetic variance ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Geriatrics ; Heart attack ; Homologous recombination ; Homology ; Humans ; Infarction ; Joining ; Linkage Disequilibrium - genetics ; Male ; Medicine ; Middle Aged ; Mismatch repair ; Myocardial infarction ; Myocardial Infarction - genetics ; Non-homologous end joining ; Nucleotide excision repair ; Older people ; Pathways ; Plaques ; Polymorphism, Single Nucleotide - genetics ; Pravastatin ; Repair ; Restenosis ; Risk ; Studies</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e56262-e56262</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Verschuren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Verschuren et al 2013 Verschuren et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1ec620f8b2f15d147dc9788a79f9c825e42c9b02bf83dcfdb22bef65b9e59ac3</citedby><cites>FETCH-LOGICAL-c692t-1ec620f8b2f15d147dc9788a79f9c825e42c9b02bf83dcfdb22bef65b9e59ac3</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/PMC3574159/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574159/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23457540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Korolev, Sergey</contributor><creatorcontrib>Verschuren, Jeffrey J W</creatorcontrib><creatorcontrib>Trompet, Stella</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Stott, David J</creatorcontrib><creatorcontrib>Sattar, Naveed</creatorcontrib><creatorcontrib>Buckley, Brendan M</creatorcontrib><creatorcontrib>Ford, Ian</creatorcontrib><creatorcontrib>Heijmans, Bastiaan T</creatorcontrib><creatorcontrib>Guchelaar, Henk-Jan</creatorcontrib><creatorcontrib>Houwing-Duistermaat, Jeanine J</creatorcontrib><creatorcontrib>Slagboom, P Eline</creatorcontrib><creatorcontrib>Jukema, J Wouter</creatorcontrib><title>Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.
The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.
The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.
This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</description><subject>Aged</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Base excision repair</subject><subject>Biology</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cell death</subject><subject>Chromosome Mapping</subject><subject>Damage accumulation</subject><subject>Defects</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Damage - genetics</subject><subject>DNA End-Joining Repair - genetics</subject><subject>DNA repair</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic research</subject><subject>Genetic variance</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Geriatrics</subject><subject>Heart attack</subject><subject>Homologous recombination</subject><subject>Homology</subject><subject>Humans</subject><subject>Infarction</subject><subject>Joining</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mismatch repair</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - genetics</subject><subject>Non-homologous end joining</subject><subject>Nucleotide excision repair</subject><subject>Older people</subject><subject>Pathways</subject><subject>Plaques</subject><subject>Polymorphism, Single Nucleotide - 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end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data</title><author>Verschuren, Jeffrey J W ; Trompet, Stella ; Deelen, Joris ; Stott, David J ; Sattar, Naveed ; Buckley, Brendan M ; Ford, Ian ; Heijmans, Bastiaan T ; Guchelaar, Henk-Jan ; Houwing-Duistermaat, Jeanine J ; Slagboom, P Eline ; Jukema, J Wouter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1ec620f8b2f15d147dc9788a79f9c825e42c9b02bf83dcfdb22bef65b9e59ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Base excision repair</topic><topic>Biology</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cell death</topic><topic>Chromosome Mapping</topic><topic>Damage accumulation</topic><topic>Defects</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA Damage - genetics</topic><topic>DNA End-Joining Repair - genetics</topic><topic>DNA repair</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genetic research</topic><topic>Genetic variance</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Geriatrics</topic><topic>Heart attack</topic><topic>Homologous recombination</topic><topic>Homology</topic><topic>Humans</topic><topic>Infarction</topic><topic>Joining</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Male</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Mismatch repair</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - genetics</topic><topic>Non-homologous 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Henk-Jan</au><au>Houwing-Duistermaat, Jeanine J</au><au>Slagboom, P Eline</au><au>Jukema, J Wouter</au><au>Korolev, Sergey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-02-15</date><risdate>2013</risdate><volume>8</volume><issue>2</issue><spage>e56262</spage><epage>e56262</epage><pages>e56262-e56262</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.
The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.
The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.
This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23457540</pmid><doi>10.1371/journal.pone.0056262</doi><tpages>e56262</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-02, Vol.8 (2), p.e56262-e56262 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1331592249 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aged Analysis Apoptosis Base excision repair Biology Cardiovascular disease Cardiovascular diseases Cell death Chromosome Mapping Damage accumulation Defects Deoxyribonucleic acid Development and progression DNA DNA damage DNA Damage - genetics DNA End-Joining Repair - genetics DNA repair Female Genes Genetic aspects Genetic diversity Genetic Predisposition to Disease - genetics Genetic research Genetic variance Genome-wide association studies Genome-Wide Association Study Genomes Genomics Geriatrics Heart attack Homologous recombination Homology Humans Infarction Joining Linkage Disequilibrium - genetics Male Medicine Middle Aged Mismatch repair Myocardial infarction Myocardial Infarction - genetics Non-homologous end joining Nucleotide excision repair Older people Pathways Plaques Polymorphism, Single Nucleotide - genetics Pravastatin Repair Restenosis Risk Studies |
| title | Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data |
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