ParkinsonCanadaV1, Main, Exploration, bibRecord, 000343

Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies

Identifieur interne : 000343 ( Main/Exploration ); précédent : 000342; suivant : 000344

Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies

Auteurs : Norrina B. Allen [États-Unis] ; Donald Lloyd-Jones [États-Unis] ; Shih-Jen Hwang [États-Unis] ; Laura Rasmussen-Torvik [États-Unis] ; Myriam Fornage [États-Unis] ; Alanna C. Morrison [États-Unis] ; Abigail S. Baldridge [États-Unis] ; Eric Boerwinkle [États-Unis] ; Daniel Levy [États-Unis] ; L. Adrienne Cupples [États-Unis] ; Caroline S. Fox [États-Unis] ; George Thanassoulis [Canada] ; Line Dufresne [Canada] ; Martha Daviglus [États-Unis] ; Andrew D. Johnson [États-Unis] ; Jared Reis [États-Unis] ; Jerome Rotter [États-Unis] ; Walter Palmas [États-Unis] ; Mathew Allison [États-Unis] ; James S. Pankow [États-Unis] ; Christopher J. O Onnell [États-Unis]

Source :

American heart journal [ 0002-8703 ] ; 2016.

RBID : PMC:4873714

Abstract

Background

Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CVD morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study (GWAS) on the trait.

Methods and Results

We examined two dichotomous phenotypes of ideal CV health - Clinical (untreated cholesterol < 200 mg/dl; untreated blood pressure (BP) <120/<80; not diabetic) and Clinical+Behavioral (Clinical plus: not a current smoker; BMI <25 kg/m²) -among white participants aged 50 ± 5 years. We performed a meta-analysis of four GWAS (total n=11,708) from the MESA, CARDIA, ARIC and Framingham Heart Study cohorts. We identified a SNP (rs445925) in the APOC1/APOE region that was associated with Clinical ideal CV health at genome-wide level of significance (p<2.0×10⁻⁹). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for LDL cholesterol.

Conclusion

A common SNP in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower cardiovascular risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873714

DOI: 10.1016/j.ahj.2015.12.022
PubMed: 27179730
PubMed Central: 4873714

Affiliations:

Canada, États-Unis
Californie, Illinois, Maryland, Massachusetts, Minnesota, Québec, Texas, État de New York
Montréal
Université McGill

Le document en format XML

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<author><name sortKey="Daviglus, Martha" sort="Daviglus, Martha" uniqKey="Daviglus M" first="Martha" last="Daviglus">Martha Daviglus</name>
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<author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name>
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<author><name sortKey="O Onnell, Christopher J" sort="O Onnell, Christopher J" uniqKey="O Onnell C" first="Christopher J." last="O Onnell">Christopher J. O Onnell</name>
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<placeName><region type="state">Massachusetts</region>
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<affiliation wicri:level="2"><nlm:aff id="A13">Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
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<wicri:cityArea>Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
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<author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C." last="Morrison">Alanna C. Morrison</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
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<author><name sortKey="Baldridge, Abigail S" sort="Baldridge, Abigail S" uniqKey="Baldridge A" first="Abigail S." last="Baldridge">Abigail S. Baldridge</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
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<author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
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<author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
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<affiliation wicri:level="2"><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>NHLBI’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cupples, L Adrienne" sort="Cupples, L Adrienne" uniqKey="Cupples L" first="L. Adrienne" last="Cupples">L. Adrienne Cupples</name>
<affiliation wicri:level="2"><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>NHLBI’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Fox, Caroline S" sort="Fox, Caroline S" uniqKey="Fox C" first="Caroline S." last="Fox">Caroline S. Fox</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>NHLBI’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Thanassoulis, George" sort="Thanassoulis, George" uniqKey="Thanassoulis G" first="George" last="Thanassoulis">George Thanassoulis</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec</wicri:regionArea>
<wicri:noRegion>Quebec</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A6">Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec</wicri:regionArea>
<orgName type="university">Université McGill</orgName>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dufresne, Line" sort="Dufresne, Line" uniqKey="Dufresne L" first="Line" last="Dufresne">Line Dufresne</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec</wicri:regionArea>
<wicri:noRegion>Quebec</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Daviglus, Martha" sort="Daviglus, Martha" uniqKey="Daviglus M" first="Martha" last="Daviglus">Martha Daviglus</name>
<affiliation wicri:level="2"><nlm:aff id="A7">University of Illinois at Chicago, IL</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>University of Illinois at Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>NHLBI’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Reis, Jared" sort="Reis, Jared" uniqKey="Reis J" first="Jared" last="Reis">Jared Reis</name>
<affiliation wicri:level="2"><nlm:aff id="A8">National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Rotter, Jerome" sort="Rotter, Jerome" uniqKey="Rotter J" first="Jerome" last="Rotter">Jerome Rotter</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Palmas, Walter" sort="Palmas, Walter" uniqKey="Palmas W" first="Walter" last="Palmas">Walter Palmas</name>
<affiliation wicri:level="2"><nlm:aff id="A10">Dept of Medicine, Columbia University, NY, NY</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Dept of Medicine, Columbia University, NY</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Allison, Mathew" sort="Allison, Mathew" uniqKey="Allison M" first="Mathew" last="Allison">Mathew Allison</name>
<affiliation wicri:level="2"><nlm:aff id="A11">Division of Preventive Medicine, University of California, San Diego, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Division of Preventive Medicine, University of California, San Diego</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Pankow, James S" sort="Pankow, James S" uniqKey="Pankow J" first="James S." last="Pankow">James S. Pankow</name>
<affiliation wicri:level="2"><nlm:aff id="A12">University of Minnesota, Minneapolis, MN</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>University of Minnesota, Minneapolis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="O Onnell, Christopher J" sort="O Onnell, Christopher J" uniqKey="O Onnell C" first="Christopher J." last="O Onnell">Christopher J. O Onnell</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>NHLBI’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A13">Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">American heart journal</title>
<idno type="ISSN">0002-8703</idno>
<idno type="eISSN">1097-6744</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CVD morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study (GWAS) on the trait.</p>
</sec>
<sec id="S2"><title>Methods and Results</title>
<p id="P2">We examined two dichotomous phenotypes of ideal CV health - Clinical (untreated cholesterol < 200 mg/dl; untreated blood pressure (BP) <120/<80; not diabetic) and Clinical+Behavioral (Clinical plus: not a current smoker; BMI <25 kg/m<sup>2</sup>
) -among white participants aged 50 ± 5 years. We performed a meta-analysis of four GWAS (total n=11,708) from the MESA, CARDIA, ARIC and Framingham Heart Study cohorts. We identified a SNP (rs445925) in the <italic>APOC1/APOE</italic>
 region that was associated with Clinical ideal CV health at genome-wide level of significance (p<2.0×10<sup>−9</sup>
). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for LDL cholesterol.</p>
</sec>
<sec id="S3"><title>Conclusion</title>
<p id="P3">A common SNP in the <italic>APOC1</italic>
/APOE region, previously found to be associated with protective levels of cholesterol and lower cardiovascular risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Illinois</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Minnesota</li>
<li>Québec</li>
<li>Texas</li>
<li>État de New York</li>
</region>
<settlement><li>Montréal</li>
</settlement>
<orgName><li>Université McGill</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Illinois"><name sortKey="Allen, Norrina B" sort="Allen, Norrina B" uniqKey="Allen N" first="Norrina B." last="Allen">Norrina B. Allen</name>
</region>
<name sortKey="Allison, Mathew" sort="Allison, Mathew" uniqKey="Allison M" first="Mathew" last="Allison">Mathew Allison</name>
<name sortKey="Baldridge, Abigail S" sort="Baldridge, Abigail S" uniqKey="Baldridge A" first="Abigail S." last="Baldridge">Abigail S. Baldridge</name>
<name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name>
<name sortKey="Cupples, L Adrienne" sort="Cupples, L Adrienne" uniqKey="Cupples L" first="L. Adrienne" last="Cupples">L. Adrienne Cupples</name>
<name sortKey="Daviglus, Martha" sort="Daviglus, Martha" uniqKey="Daviglus M" first="Martha" last="Daviglus">Martha Daviglus</name>
<name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name>
<name sortKey="Fox, Caroline S" sort="Fox, Caroline S" uniqKey="Fox C" first="Caroline S." last="Fox">Caroline S. Fox</name>
<name sortKey="Fox, Caroline S" sort="Fox, Caroline S" uniqKey="Fox C" first="Caroline S." last="Fox">Caroline S. Fox</name>
<name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name>
<name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name>
<name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name>
<name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name>
<name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name>
<name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name>
<name sortKey="Lloyd Jones, Donald" sort="Lloyd Jones, Donald" uniqKey="Lloyd Jones D" first="Donald" last="Lloyd-Jones">Donald Lloyd-Jones</name>
<name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C." last="Morrison">Alanna C. Morrison</name>
<name sortKey="O Onnell, Christopher J" sort="O Onnell, Christopher J" uniqKey="O Onnell C" first="Christopher J." last="O Onnell">Christopher J. O Onnell</name>
<name sortKey="O Onnell, Christopher J" sort="O Onnell, Christopher J" uniqKey="O Onnell C" first="Christopher J." last="O Onnell">Christopher J. O Onnell</name>
<name sortKey="O Onnell, Christopher J" sort="O Onnell, Christopher J" uniqKey="O Onnell C" first="Christopher J." last="O Onnell">Christopher J. O Onnell</name>
<name sortKey="Palmas, Walter" sort="Palmas, Walter" uniqKey="Palmas W" first="Walter" last="Palmas">Walter Palmas</name>
<name sortKey="Pankow, James S" sort="Pankow, James S" uniqKey="Pankow J" first="James S." last="Pankow">James S. Pankow</name>
<name sortKey="Rasmussen Torvik, Laura" sort="Rasmussen Torvik, Laura" uniqKey="Rasmussen Torvik L" first="Laura" last="Rasmussen-Torvik">Laura Rasmussen-Torvik</name>
<name sortKey="Reis, Jared" sort="Reis, Jared" uniqKey="Reis J" first="Jared" last="Reis">Jared Reis</name>
<name sortKey="Rotter, Jerome" sort="Rotter, Jerome" uniqKey="Rotter J" first="Jerome" last="Rotter">Jerome Rotter</name>
</country>
<country name="Canada"><noRegion><name sortKey="Thanassoulis, George" sort="Thanassoulis, George" uniqKey="Thanassoulis G" first="George" last="Thanassoulis">George Thanassoulis</name>
</noRegion>
<name sortKey="Dufresne, Line" sort="Dufresne, Line" uniqKey="Dufresne L" first="Line" last="Dufresne">Line Dufresne</name>
<name sortKey="Thanassoulis, George" sort="Thanassoulis, George" uniqKey="Thanassoulis G" first="George" last="Thanassoulis">George Thanassoulis</name>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies

Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies

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