Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe
Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical...
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| description | Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition. |
| doi_str_mv | 10.1371/journal.pone.0096504 |
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This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0096504</identifier><identifier>PMID: 24806096</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Coronary artery ; Coronary artery disease ; Coronary Artery Disease - epidemiology ; Coronary Artery Disease - genetics ; Coronary diseases ; Environmental factors ; Epidemiology ; Europe - epidemiology ; Female ; Genes ; Genetic aspects ; Genetic polymorphisms ; Genetic Predisposition to Disease ; Genetics ; Genètica de poblacions ; Genètica humana ; Health aspects ; Health risk assessment ; Heart attack ; Heart diseases ; Human genetics ; Humans ; Incidence ; Malalties coronàries ; Male ; Medicine and Health Sciences ; Morbidity ; Mortality ; Myocardial infarction ; Myocardial Infarction - genetics ; Nitric oxide ; Nitric Oxide Synthase - genetics ; Nitric-oxide synthase ; Polimorfisme genètic ; Polymorphism, Single Nucleotide ; Population Genetics ; Populations ; Public health ; Risk analysis ; Risk factors ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Studies ; Subpopulations ; Òxid nítric</subject><ispartof>PloS one, 2014-05, Vol.9 (5), p.e96504</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Carreras-Torres et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://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>cc-by (c) Carreras Torres, Robert et al., 2014 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a></rights><rights>2014 Carreras-Torres et al 2014 Carreras-Torres et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c734t-74d784835aaeb0c1733a1c1d60e9639af87e5462b152f84e4552e3fd242bc28e3</citedby><cites>FETCH-LOGICAL-c734t-74d784835aaeb0c1733a1c1d60e9639af87e5462b152f84e4552e3fd242bc28e3</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/PMC4013019/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013019/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,26951,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24806096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Dubé, Marie-Pierre</contributor><creatorcontrib>Carreras-Torres, Robert</creatorcontrib><creatorcontrib>Kundu, Suman</creatorcontrib><creatorcontrib>Zanetti, Daniela</creatorcontrib><creatorcontrib>Esteban, Esther</creatorcontrib><creatorcontrib>Via, Marc</creatorcontrib><creatorcontrib>Moral, Pedro</creatorcontrib><title>Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.</description><subject>Biology and Life Sciences</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary diseases</subject><subject>Environmental factors</subject><subject>Epidemiology</subject><subject>Europe - epidemiology</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genètica de poblacions</subject><subject>Genètica humana</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Heart attack</subject><subject>Heart diseases</subject><subject>Human genetics</subject><subject>Humans</subject><subject>Incidence</subject><subject>Malalties coronàries</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - genetics</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Nitric-oxide synthase</subject><subject>Polimorfisme genètic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population Genetics</subject><subject>Populations</subject><subject>Public health</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Subpopulations</subject><subject>Òxid nítric</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>XX2</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYqPwHyCwhITEQ4t_JU5ekKZpjEoTlRjwarn2pXVJ4852Bnvhb8dZs6qRQEJJ5Nj3-Z7P57sse0nwjDBB3m9c51vVzHauhRnGVZFj_ig7JRWj04Ji9vjo_yR7FsIG45yVRfE0O6G8xEWSnGa_L6GFaDXyNvxAQTsPyNXo8-IarZIF3SpvVRsDUiE4bVUEg37auEbbO6eVN1Y1yLa18jpa16Kk99AkKuypNHet8neJ0dZAqwEp7V0I6KLzbgfPsye1agK8GMZJ9u3jxdfzT9OrxeX8_OxqqgXjcSq4ESUvWa4ULLEmgjFFNDEFhqpglapLATkv6JLktC458DynwGpDOV1qWgKbZK_3fneNC3JIXZAJp4TjileJmO8J49RG7rzdprClU1beLzi_ksqnRDUglxUm2gjCK1NwzFlVGCOMKnKOdbKw5OvDsFu33ILR0EavmpHTsaW1a7lyt5JjwjDpgyF7Bzp0WnrQ4LWK98LDpP8oFlRSgYtKJM2bYVPvbjoI8R_HHKiVSidJN-dSAHprg5ZnnJQClyy9k2z2Fyo9BrZWp4KrbVofCd6NBImJ8CuuVBeCnF9_-X928X3Mvj1i16CauA6u6fpiC2OQDxnrq8tDfcg2wbLvl4dsyL5f5NAvSfbq-KYOoocGYX8As4QRFA</recordid><startdate>20140507</startdate><enddate>20140507</enddate><creator>Carreras-Torres, Robert</creator><creator>Kundu, Suman</creator><creator>Zanetti, Daniela</creator><creator>Esteban, Esther</creator><creator>Via, Marc</creator><creator>Moral, Pedro</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>XX2</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140507</creationdate><title>Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe</title><author>Carreras-Torres, Robert ; Kundu, Suman ; Zanetti, Daniela ; Esteban, Esther ; Via, Marc ; Moral, Pedro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c734t-74d784835aaeb0c1733a1c1d60e9639af87e5462b152f84e4552e3fd242bc28e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Biology and Life Sciences</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary diseases</topic><topic>Environmental factors</topic><topic>Epidemiology</topic><topic>Europe - epidemiology</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Genètica de poblacions</topic><topic>Genètica humana</topic><topic>Health aspects</topic><topic>Health risk assessment</topic><topic>Heart attack</topic><topic>Heart diseases</topic><topic>Human genetics</topic><topic>Humans</topic><topic>Incidence</topic><topic>Malalties coronàries</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - genetics</topic><topic>Nitric oxide</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Nitric-oxide synthase</topic><topic>Polimorfisme genètic</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population Genetics</topic><topic>Populations</topic><topic>Public health</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Studies</topic><topic>Subpopulations</topic><topic>Òxid nítric</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carreras-Torres, Robert</creatorcontrib><creatorcontrib>Kundu, Suman</creatorcontrib><creatorcontrib>Zanetti, Daniela</creatorcontrib><creatorcontrib>Esteban, Esther</creatorcontrib><creatorcontrib>Via, Marc</creatorcontrib><creatorcontrib>Moral, Pedro</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: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24806096</pmid><doi>10.1371/journal.pone.0096504</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biology and Life Sciences Coronary artery Coronary artery disease Coronary Artery Disease - epidemiology Coronary Artery Disease - genetics Coronary diseases Environmental factors Epidemiology Europe - epidemiology Female Genes Genetic aspects Genetic polymorphisms Genetic Predisposition to Disease Genetics Genètica de poblacions Genètica humana Health aspects Health risk assessment Heart attack Heart diseases Human genetics Humans Incidence Malalties coronàries Male Medicine and Health Sciences Morbidity Mortality Myocardial infarction Myocardial Infarction - genetics Nitric oxide Nitric Oxide Synthase - genetics Nitric-oxide synthase Polimorfisme genètic Polymorphism, Single Nucleotide Population Genetics Populations Public health Risk analysis Risk factors Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Subpopulations Òxid nítric |
| title | Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe |
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