Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies
Identifieur interne : 000706 ( Pmc/Corpus ); précédent : 000705; suivant : 000707Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies
Auteurs : Norrina B. Allen ; Donald Lloyd-Jones ; Shih-Jen Hwang ; Laura Rasmussen-Torvik ; Myriam Fornage ; Alanna C. Morrison ; Abigail S. Baldridge ; Eric Boerwinkle ; Daniel Levy ; L. Adrienne Cupples ; Caroline S. Fox ; George Thanassoulis ; Line Dufresne ; Martha Daviglus ; Andrew D. Johnson ; Jared Reis ; Jerome Rotter ; Walter Palmas ; Mathew Allison ; James S. Pankow ; Christopher J. O OnnellSource :
- American heart journal [ 0002-8703 ] ; 2016.
Abstract
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.
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
A common SNP in the
Url:
DOI: 10.1016/j.ahj.2015.12.022
PubMed: 27179730
PubMed Central: 4873714
Links to Exploration step
PMC:4873714Le document en format XML
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Allen</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Lloyd Jones, Donald" sort="Lloyd Jones, Donald" uniqKey="Lloyd Jones D" first="Donald" last="Lloyd-Jones">Donald Lloyd-Jones</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><affiliation><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation></author><author><name sortKey="Rasmussen Torvik, Laura" sort="Rasmussen Torvik, Laura" uniqKey="Rasmussen Torvik L" first="Laura" last="Rasmussen-Torvik">Laura Rasmussen-Torvik</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="A4">Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C." last="Morrison">Alanna C. Morrison</name><affiliation><nlm:aff id="A4">Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Baldridge, Abigail S" sort="Baldridge, Abigail S" uniqKey="Baldridge A" first="Abigail S." last="Baldridge">Abigail S. Baldridge</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="A4">Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><affiliation><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></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><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></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><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation></author><author><name sortKey="Thanassoulis, George" sort="Thanassoulis, George" uniqKey="Thanassoulis G" first="George" last="Thanassoulis">George Thanassoulis</name><affiliation><nlm:aff id="A5">Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Dufresne, Line" sort="Dufresne, Line" uniqKey="Dufresne L" first="Line" last="Dufresne">Line Dufresne</name><affiliation><nlm:aff id="A5">Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Daviglus, Martha" sort="Daviglus, Martha" uniqKey="Daviglus M" first="Martha" last="Daviglus">Martha Daviglus</name><affiliation><nlm:aff id="A7">University of Illinois at Chicago, IL</nlm:aff></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><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation></author><author><name sortKey="Reis, Jared" sort="Reis, Jared" uniqKey="Reis J" first="Jared" last="Reis">Jared Reis</name><affiliation><nlm:aff id="A8">National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome" sort="Rotter, Jerome" uniqKey="Rotter J" first="Jerome" last="Rotter">Jerome Rotter</name><affiliation><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></affiliation></author><author><name sortKey="Palmas, Walter" sort="Palmas, Walter" uniqKey="Palmas W" first="Walter" last="Palmas">Walter Palmas</name><affiliation><nlm:aff id="A10">Dept of Medicine, Columbia University, NY, NY</nlm:aff></affiliation></author><author><name sortKey="Allison, Mathew" sort="Allison, Mathew" uniqKey="Allison M" first="Mathew" last="Allison">Mathew Allison</name><affiliation><nlm:aff id="A11">Division of Preventive Medicine, University of California, San Diego, CA</nlm:aff></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><nlm:aff id="A12">University of Minnesota, Minneapolis, MN</nlm:aff></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><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27179730</idno><idno type="pmc">4873714</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873714</idno><idno type="RBID">PMC:4873714</idno><idno type="doi">10.1016/j.ahj.2015.12.022</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000706</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000706</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies</title><author><name sortKey="Allen, Norrina B" sort="Allen, Norrina B" uniqKey="Allen N" first="Norrina B." last="Allen">Norrina B. Allen</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Lloyd Jones, Donald" sort="Lloyd Jones, Donald" uniqKey="Lloyd Jones D" first="Donald" last="Lloyd-Jones">Donald Lloyd-Jones</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><affiliation><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation></author><author><name sortKey="Rasmussen Torvik, Laura" sort="Rasmussen Torvik, Laura" uniqKey="Rasmussen Torvik L" first="Laura" last="Rasmussen-Torvik">Laura Rasmussen-Torvik</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="A4">Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C." last="Morrison">Alanna C. Morrison</name><affiliation><nlm:aff id="A4">Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Baldridge, Abigail S" sort="Baldridge, Abigail S" uniqKey="Baldridge A" first="Abigail S." last="Baldridge">Abigail S. Baldridge</name><affiliation><nlm:aff id="A1">Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="A4">Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><affiliation><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></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><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></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><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation></author><author><name sortKey="Thanassoulis, George" sort="Thanassoulis, George" uniqKey="Thanassoulis G" first="George" last="Thanassoulis">George Thanassoulis</name><affiliation><nlm:aff id="A5">Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Dufresne, Line" sort="Dufresne, Line" uniqKey="Dufresne L" first="Line" last="Dufresne">Line Dufresne</name><affiliation><nlm:aff id="A5">Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Daviglus, Martha" sort="Daviglus, Martha" uniqKey="Daviglus M" first="Martha" last="Daviglus">Martha Daviglus</name><affiliation><nlm:aff id="A7">University of Illinois at Chicago, IL</nlm:aff></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><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation></author><author><name sortKey="Reis, Jared" sort="Reis, Jared" uniqKey="Reis J" first="Jared" last="Reis">Jared Reis</name><affiliation><nlm:aff id="A8">National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome" sort="Rotter, Jerome" uniqKey="Rotter J" first="Jerome" last="Rotter">Jerome Rotter</name><affiliation><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></affiliation></author><author><name sortKey="Palmas, Walter" sort="Palmas, Walter" uniqKey="Palmas W" first="Walter" last="Palmas">Walter Palmas</name><affiliation><nlm:aff id="A10">Dept of Medicine, Columbia University, NY, NY</nlm:aff></affiliation></author><author><name sortKey="Allison, Mathew" sort="Allison, Mathew" uniqKey="Allison M" first="Mathew" last="Allison">Mathew Allison</name><affiliation><nlm:aff id="A11">Division of Preventive Medicine, University of California, San Diego, CA</nlm:aff></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><nlm:aff id="A12">University of Minnesota, Minneapolis, MN</nlm:aff></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><nlm:aff id="A2">Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">NHLBI’s Framingham Heart Study, Framingham, MA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA</nlm:aff></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><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0370465</journal-id><journal-id journal-id-type="pubmed-jr-id">398</journal-id><journal-id journal-id-type="nlm-ta">Am Heart J</journal-id><journal-id journal-id-type="iso-abbrev">Am. Heart J.</journal-id><journal-title-group><journal-title>American heart journal</journal-title></journal-title-group><issn pub-type="ppub">0002-8703</issn><issn pub-type="epub">1097-6744</issn></journal-meta><article-meta><article-id pub-id-type="pmid">27179730</article-id><article-id pub-id-type="pmc">4873714</article-id><article-id pub-id-type="doi">10.1016/j.ahj.2015.12.022</article-id><article-id pub-id-type="manuscript">NIHMS754413</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Allen</surname><given-names>Norrina B.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lloyd-Jones</surname><given-names>Donald</given-names></name><degrees>MD, ScM</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hwang</surname><given-names>Shih-Jen</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rasmussen-Torvik</surname><given-names>Laura</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Fornage</surname><given-names>Myriam</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Morrison</surname><given-names>Alanna C.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Baldridge</surname><given-names>Abigail S.</given-names></name><degrees>MSEB</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Boerwinkle</surname><given-names>Eric</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Levy</surname><given-names>Daniel</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cupples</surname><given-names>L. Adrienne</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Fox</surname><given-names>Caroline S.</given-names></name><degrees>MD, MPH</degrees><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Thanassoulis</surname><given-names>George</given-names></name><degrees>MD MSc</degrees><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Dufresne</surname><given-names>Line</given-names></name><degrees>MSc</degrees><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Daviglus</surname><given-names>Martha</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Andrew D.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Reis</surname><given-names>Jared</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Rotter</surname><given-names>Jerome</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Palmas</surname><given-names>Walter</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Allison</surname><given-names>Mathew</given-names></name><degrees>MD, MPH</degrees><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Pankow</surname><given-names>James S.</given-names></name><degrees>PhD, MPH</degrees><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>O’Donnell</surname><given-names>Christopher J.</given-names></name><degrees>MD, MPH</degrees><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A13">13</xref></contrib></contrib-group><aff id="A1"><label>1</label>Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL</aff><aff id="A2"><label>2</label>Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), Framingham, MA</aff><aff id="A3"><label>3</label>NHLBI’s Framingham Heart Study, Framingham, MA</aff><aff id="A4"><label>4</label>Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</aff><aff id="A5"><label>5</label>Department of Medicine and the Research Institute, Preventive and Genomic Cardiology, McGill University Health Center, Montreal, Quebec, Canada</aff><aff id="A6"><label>6</label>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</aff><aff id="A7"><label>7</label>University of Illinois at Chicago, IL</aff><aff id="A8"><label>8</label>National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD</aff><aff id="A9"><label>9</label>Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA</aff><aff id="A10"><label>10</label>Dept of Medicine, Columbia University, NY, NY</aff><aff id="A11"><label>11</label>Division of Preventive Medicine, University of California, San Diego, CA</aff><aff id="A12"><label>12</label>University of Minnesota, Minneapolis, MN</aff><aff id="A13"><label>13</label>Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA</aff><author-notes><corresp id="cor1"><bold>Corresponding author:</bold> Norrina Allen, PhD, MPH, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N Lake Shore Dr, Suite1400, Chicago, Illinois 60611, 312.503.3438 office, 312.908.9588 fax, <email>Norrina-allen@northwestern.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>29</day><month>1</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>23</day><month>1</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>5</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>5</month><year>2017</year></pub-date><volume>175</volume><fpage>112</fpage><lpage>120</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.ahj.2015.12.022</pmc-comment>
<abstract><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></abstract><kwd-group><kwd>cardiovascular diseases</kwd><kwd>genetics</kwd><kwd>epidemiology</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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