AustralieFrV1, Main, Exploration, bibRecord, 002859

Runs of Homozygosity: Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages

Identifieur interne : 002859 ( Main/Exploration ); précédent : 002858; suivant : 002860

Runs of Homozygosity: Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages

Auteurs : Paraskevi Christofidou [Royaume-Uni] ; Christopher P. Nelson [Royaume-Uni] ; Majid Nikpay [Canada] ; Liming Qu [États-Unis] ; Mingyao Li [États-Unis] ; Christina Loley [Allemagne] ; Radoslaw Debiec [Royaume-Uni] ; Peter S. Braund [Royaume-Uni] ; Matthew Denniff [Royaume-Uni] ; Fadi J. Charchar [Australie] ; Ares Rocanin Arjo [France] ; David-Alexandre Trégouët [France] ; Alison H. Goodall [Royaume-Uni] ; Francois Cambien [France] ; Willem H. Ouwehand [Royaume-Uni] ; Robert Roberts [Canada] ; Heribert Schunkert [Allemagne] ; Christian Hengstenberg [Allemagne] ; Muredach P. Reilly [États-Unis] ; Jeanette Erdmann [Allemagne] ; Ruth Mcpherson [Canada] ; Inke R. König [Allemagne] ; John R. Thompson [Royaume-Uni] ; Nilesh J. Samani [Royaume-Uni] ; Maciej Tomaszewski [Royaume-Uni]

Source :

American Journal of Human Genetics [ 0002-9297 ] ; 2015.

RBID : PMC:4573243

Descripteurs français

KwdFr :
- ARN messager (métabolisme), Facteurs de l'âge, Gènes récessifs (génétique), Homozygote, Humains, Macrophages (métabolisme), Maladie des artères coronaires (génétique), Monocytes (métabolisme), Population d'origine européenne (génétique), Régulation de l'expression des gènes (génétique).
MESH :
- génétique : Gènes récessifs, Maladie des artères coronaires, Population d'origine européenne, Régulation de l'expression des gènes.
- métabolisme : ARN messager, Macrophages, Monocytes.
- Facteurs de l'âge, Homozygote, Humains.

English descriptors

KwdEn :
- Age Factors, Coronary Artery Disease (genetics), European Continental Ancestry Group (genetics), Gene Expression Regulation (genetics), Genes, Recessive (genetics), Homozygote, Humans, Macrophages (metabolism), Monocytes (metabolism), RNA, Messenger (metabolism).
MESH :
- chemical , metabolism : RNA, Messenger.
- genetics : Coronary Artery Disease, European Continental Ancestry Group, Gene Expression Regulation, Genes, Recessive.
- metabolism : Macrophages, Monocytes.
- Age Factors, Homozygote, Humans.

Abstract

Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4–0.8) excess of ROHs when compared to coronary-artery-disease-free control subjects (p = 1.49 × 10⁻⁹). The average total length of ROHs was approximately 1,046.92 (95% CI: 634.4–1,459.5) kb greater in individuals with coronary artery disease than control subjects (p = 6.61 × 10⁻⁷). None of the identified individual ROHs was associated with coronary artery disease after correction for multiple testing. However, in aggregate burden analysis, ROHs favoring increased risk of coronary artery disease were much more common than those showing the opposite direction of association with coronary artery disease (p = 2.69 × 10⁻³³). Individual ROHs showed significant associations with monocyte and macrophage expression of genes in their close proximity—subjects with several individual ROHs showed significant differences in the expression of 44 mRNAs in monocytes and 17 mRNAs in macrophages when compared to subjects without those ROHs. This study provides evidence for an excess of homozygosity in coronary artery disease in outbred populations and suggest the potential biological relevance of ROHs in cells of importance to the pathogenesis of atherosclerosis.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573243

DOI: 10.1016/j.ajhg.2015.06.001
PubMed: 26166477
PubMed Central: 4573243

Affiliations:

Le document en format XML

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<author><name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
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<author><name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H." last="Ouwehand">Willem H. Ouwehand</name>
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<wicri:regionArea>Department of Haematology, Cambridge Biomedical Campus, University of Cambridge and NHS Blood and Transplant, Cambridge CB2 0PT</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="aff12">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK</nlm:aff>
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<author><name sortKey="Roberts, Robert" sort="Roberts, Robert" uniqKey="Roberts R" first="Robert" last="Roberts">Robert Roberts</name>
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<affiliation wicri:level="1"><nlm:aff id="aff4">Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5, Canada</nlm:aff>
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<wicri:regionArea>Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5</wicri:regionArea>
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<author><name sortKey="Schunkert, Heribert" sort="Schunkert, Heribert" uniqKey="Schunkert H" first="Heribert" last="Schunkert">Heribert Schunkert</name>
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<affiliation wicri:level="3"><nlm:aff id="aff14">Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636, Germany</nlm:aff>
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<author><name sortKey="Hengstenberg, Christian" sort="Hengstenberg, Christian" uniqKey="Hengstenberg C" first="Christian" last="Hengstenberg">Christian Hengstenberg</name>
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<affiliation wicri:level="3"><nlm:aff id="aff14">Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636, Germany</nlm:aff>
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<wicri:regionArea>Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636</wicri:regionArea>
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<author><name sortKey="Reilly, Muredach P" sort="Reilly, Muredach P" uniqKey="Reilly M" first="Muredach P." last="Reilly">Muredach P. Reilly</name>
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<author><name sortKey="Erdmann, Jeanette" sort="Erdmann, Jeanette" uniqKey="Erdmann J" first="Jeanette" last="Erdmann">Jeanette Erdmann</name>
<affiliation wicri:level="1"><nlm:aff id="aff16">Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck 23562, Germany</nlm:aff>
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<wicri:regionArea>Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck 23562</wicri:regionArea>
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<author><name sortKey="Mcpherson, Ruth" sort="Mcpherson, Ruth" uniqKey="Mcpherson R" first="Ruth" last="Mcpherson">Ruth Mcpherson</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7</wicri:regionArea>
<wicri:noRegion>ON K1Y 4W7</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="aff4">Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5</wicri:regionArea>
<wicri:noRegion>ON K1Y 3V5</wicri:noRegion>
</affiliation>
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<author><name sortKey="Konig, Inke R" sort="Konig, Inke R" uniqKey="Konig I" first="Inke R." last="König">Inke R. König</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562</wicri:regionArea>
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<author><name sortKey="Thompson, John R" sort="Thompson, John R" uniqKey="Thompson J" first="John R." last="Thompson">John R. Thompson</name>
<affiliation wicri:level="1"><nlm:aff id="aff17">Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Health Sciences, University of Leicester, Leicester LE1 7RH</wicri:regionArea>
<wicri:noRegion>Leicester LE1 7RH</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J." last="Samani">Nilesh J. Samani</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP</wicri:regionArea>
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</affiliation>
</author>
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<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Runs of Homozygosity: Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages</title>
<author><name sortKey="Christofidou, Paraskevi" sort="Christofidou, Paraskevi" uniqKey="Christofidou P" first="Paraskevi" last="Christofidou">Paraskevi Christofidou</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nelson, Christopher P" sort="Nelson, Christopher P" uniqKey="Nelson C" first="Christopher P." last="Nelson">Christopher P. Nelson</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nikpay, Majid" sort="Nikpay, Majid" uniqKey="Nikpay M" first="Majid" last="Nikpay">Majid Nikpay</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7</wicri:regionArea>
<wicri:noRegion>ON K1Y 4W7</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4">Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5</wicri:regionArea>
<wicri:noRegion>ON K1Y 3V5</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Qu, Liming" sort="Qu, Liming" uniqKey="Qu L" first="Liming" last="Qu">Liming Qu</name>
<affiliation wicri:level="2"><nlm:aff id="aff5">Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Mingyao" sort="Li, Mingyao" uniqKey="Li M" first="Mingyao" last="Li">Mingyao Li</name>
<affiliation wicri:level="2"><nlm:aff id="aff5">Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Loley, Christina" sort="Loley, Christina" uniqKey="Loley C" first="Christina" last="Loley">Christina Loley</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562</wicri:regionArea>
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<wicri:noRegion>23562</wicri:noRegion>
<wicri:noRegion>Lübeck 23562</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Debiec, Radoslaw" sort="Debiec, Radoslaw" uniqKey="Debiec R" first="Radoslaw" last="Debiec">Radoslaw Debiec</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Braund, Peter S" sort="Braund, Peter S" uniqKey="Braund P" first="Peter S." last="Braund">Peter S. Braund</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Denniff, Matthew" sort="Denniff, Matthew" uniqKey="Denniff M" first="Matthew" last="Denniff">Matthew Denniff</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Charchar, Fadi J" sort="Charchar, Fadi J" uniqKey="Charchar F" first="Fadi J." last="Charchar">Fadi J. Charchar</name>
<affiliation wicri:level="1"><nlm:aff id="aff7">Faculty of Science and Technology, School of Applied and Biomedical Sciences, Federation University Australia, Ballarat, VIC 3350, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Faculty of Science and Technology, School of Applied and Biomedical Sciences, Federation University Australia, Ballarat, VIC 3350</wicri:regionArea>
<wicri:noRegion>VIC 3350</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Arjo, Ares Rocanin" sort="Arjo, Ares Rocanin" uniqKey="Arjo A" first="Ares Rocanin" last="Arjo">Ares Rocanin Arjo</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">ICAN Institute for Cardiometabolism and Nutrition, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrition, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013</wicri:regionArea>
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<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10">Sorbonne Universités, UPMC University, Paris 06, UMR_S 1166, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC University, Paris 06, UMR_S 1166, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">ICAN Institute for Cardiometabolism and Nutrition, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrition, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10">Sorbonne Universités, UPMC University, Paris 06, UMR_S 1166, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC University, Paris 06, UMR_S 1166, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H." last="Goodall">Alison H. Goodall</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">ICAN Institute for Cardiometabolism and Nutrition, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrition, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013</wicri:regionArea>
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<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10">Sorbonne Universités, UPMC University, Paris 06, UMR_S 1166, Paris 75013, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC University, Paris 06, UMR_S 1166, Paris 75013</wicri:regionArea>
<wicri:noRegion>75013</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H." last="Ouwehand">Willem H. Ouwehand</name>
<affiliation wicri:level="1"><nlm:aff id="aff11">Department of Haematology, Cambridge Biomedical Campus, University of Cambridge and NHS Blood and Transplant, Cambridge CB2 0PT, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, Cambridge Biomedical Campus, University of Cambridge and NHS Blood and Transplant, Cambridge CB2 0PT</wicri:regionArea>
<wicri:noRegion>Cambridge CB2 0PT</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff12">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH</wicri:regionArea>
<wicri:noRegion>Cambridge CB10 1HH</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Roberts, Robert" sort="Roberts, Robert" uniqKey="Roberts R" first="Robert" last="Roberts">Robert Roberts</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7</wicri:regionArea>
<wicri:noRegion>ON K1Y 4W7</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4">Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5</wicri:regionArea>
<wicri:noRegion>ON K1Y 3V5</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schunkert, Heribert" sort="Schunkert, Heribert" uniqKey="Schunkert H" first="Heribert" last="Schunkert">Heribert Schunkert</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Deutsches Herzzentrum München, Technische Universität München, Munich 80636</wicri:regionArea>
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<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université technique de Munich</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff14">Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hengstenberg, Christian" sort="Hengstenberg, Christian" uniqKey="Hengstenberg C" first="Christian" last="Hengstenberg">Christian Hengstenberg</name>
<affiliation wicri:level="4"><nlm:aff id="aff13">Deutsches Herzzentrum München, Technische Universität München, Munich 80636, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Deutsches Herzzentrum München, Technische Universität München, Munich 80636</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université technique de Munich</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff14">Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK), Munich 80636</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Reilly, Muredach P" sort="Reilly, Muredach P" uniqKey="Reilly M" first="Muredach P." last="Reilly">Muredach P. Reilly</name>
<affiliation wicri:level="2"><nlm:aff id="aff15">Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19148, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19148</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Erdmann, Jeanette" sort="Erdmann, Jeanette" uniqKey="Erdmann J" first="Jeanette" last="Erdmann">Jeanette Erdmann</name>
<affiliation wicri:level="1"><nlm:aff id="aff16">Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck 23562, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck 23562</wicri:regionArea>
<wicri:noRegion>23562</wicri:noRegion>
<wicri:noRegion>23562</wicri:noRegion>
<wicri:noRegion>Lübeck 23562</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mcpherson, Ruth" sort="Mcpherson, Ruth" uniqKey="Mcpherson R" first="Ruth" last="Mcpherson">Ruth Mcpherson</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Ruddy Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7</wicri:regionArea>
<wicri:noRegion>ON K1Y 4W7</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4">Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 3V5</wicri:regionArea>
<wicri:noRegion>ON K1Y 3V5</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Konig, Inke R" sort="Konig, Inke R" uniqKey="Konig I" first="Inke R." last="König">Inke R. König</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck 23562</wicri:regionArea>
<wicri:noRegion>23562</wicri:noRegion>
<wicri:noRegion>23562</wicri:noRegion>
<wicri:noRegion>Lübeck 23562</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Thompson, John R" sort="Thompson, John R" uniqKey="Thompson J" first="John R." last="Thompson">John R. Thompson</name>
<affiliation wicri:level="1"><nlm:aff id="aff17">Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Health Sciences, University of Leicester, Leicester LE1 7RH</wicri:regionArea>
<wicri:noRegion>Leicester LE1 7RH</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J." last="Samani">Nilesh J. Samani</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester LE3 9QP</wicri:regionArea>
<wicri:noRegion>Leicester LE3 9QP</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="eISSN">1537-6605</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age Factors</term>
<term>Coronary Artery Disease (genetics)</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Gene Expression Regulation (genetics)</term>
<term>Genes, Recessive (genetics)</term>
<term>Homozygote</term>
<term>Humans</term>
<term>Macrophages (metabolism)</term>
<term>Monocytes (metabolism)</term>
<term>RNA, Messenger (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (métabolisme)</term>
<term>Facteurs de l'âge</term>
<term>Gènes récessifs (génétique)</term>
<term>Homozygote</term>
<term>Humains</term>
<term>Macrophages (métabolisme)</term>
<term>Maladie des artères coronaires (génétique)</term>
<term>Monocytes (métabolisme)</term>
<term>Population d'origine européenne (génétique)</term>
<term>Régulation de l'expression des gènes (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronary Artery Disease</term>
<term>European Continental Ancestry Group</term>
<term>Gene Expression Regulation</term>
<term>Genes, Recessive</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Gènes récessifs</term>
<term>Maladie des artères coronaires</term>
<term>Population d'origine européenne</term>
<term>Régulation de l'expression des gènes</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Macrophages</term>
<term>Monocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN messager</term>
<term>Macrophages</term>
<term>Monocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Age Factors</term>
<term>Homozygote</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Facteurs de l'âge</term>
<term>Homozygote</term>
<term>Humains</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4<bold>–</bold>
0.8) excess of ROHs when compared to coronary-artery-disease<bold>-</bold>
free control subjects (p = 1.49 × 10<sup>−9</sup>
). The average total length of ROHs was approximately 1,046.92 (95% CI: 634.4<bold>–</bold>
1,459.5) kb greater in individuals with coronary artery disease than control subjects (p = 6.61 × 10<sup>−7</sup>
). None of the identified individual ROHs was associated with coronary artery disease after correction for multiple testing. However, in aggregate burden analysis, ROHs favoring increased risk of coronary artery disease were much more common than those showing the opposite direction of association with coronary artery disease (p = 2.69 × 10<sup>−33</sup>
). Individual ROHs showed significant associations with monocyte and macrophage expression of genes in their close proximity—subjects with several individual ROHs showed significant differences in the expression of 44 mRNAs in monocytes and 17 mRNAs in macrophages when compared to subjects without those ROHs. This study provides evidence for an excess of homozygosity in coronary artery disease in outbred populations and suggest the potential biological relevance of ROHs in cells of importance to the pathogenesis of atherosclerosis.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Bavière</li>
<li>District de Haute-Bavière</li>
<li>Pennsylvanie</li>
<li>Île-de-France</li>
</region>
<settlement><li>Munich</li>
<li>Paris</li>
</settlement>
<orgName><li>Université technique de Munich</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Christofidou, Paraskevi" sort="Christofidou, Paraskevi" uniqKey="Christofidou P" first="Paraskevi" last="Christofidou">Paraskevi Christofidou</name>
</noRegion>
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<name sortKey="Denniff, Matthew" sort="Denniff, Matthew" uniqKey="Denniff M" first="Matthew" last="Denniff">Matthew Denniff</name>
<name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H." last="Goodall">Alison H. Goodall</name>
<name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H." last="Goodall">Alison H. Goodall</name>
<name sortKey="Nelson, Christopher P" sort="Nelson, Christopher P" uniqKey="Nelson C" first="Christopher P." last="Nelson">Christopher P. Nelson</name>
<name sortKey="Nelson, Christopher P" sort="Nelson, Christopher P" uniqKey="Nelson C" first="Christopher P." last="Nelson">Christopher P. Nelson</name>
<name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H." last="Ouwehand">Willem H. Ouwehand</name>
<name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H." last="Ouwehand">Willem H. Ouwehand</name>
<name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J." last="Samani">Nilesh J. Samani</name>
<name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J." last="Samani">Nilesh J. Samani</name>
<name sortKey="Thompson, John R" sort="Thompson, John R" uniqKey="Thompson J" first="John R." last="Thompson">John R. Thompson</name>
<name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name>
<name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name>
</country>
<country name="Canada"><noRegion><name sortKey="Nikpay, Majid" sort="Nikpay, Majid" uniqKey="Nikpay M" first="Majid" last="Nikpay">Majid Nikpay</name>
</noRegion>
<name sortKey="Mcpherson, Ruth" sort="Mcpherson, Ruth" uniqKey="Mcpherson R" first="Ruth" last="Mcpherson">Ruth Mcpherson</name>
<name sortKey="Mcpherson, Ruth" sort="Mcpherson, Ruth" uniqKey="Mcpherson R" first="Ruth" last="Mcpherson">Ruth Mcpherson</name>
<name sortKey="Nikpay, Majid" sort="Nikpay, Majid" uniqKey="Nikpay M" first="Majid" last="Nikpay">Majid Nikpay</name>
<name sortKey="Roberts, Robert" sort="Roberts, Robert" uniqKey="Roberts R" first="Robert" last="Roberts">Robert Roberts</name>
<name sortKey="Roberts, Robert" sort="Roberts, Robert" uniqKey="Roberts R" first="Robert" last="Roberts">Robert Roberts</name>
</country>
<country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Qu, Liming" sort="Qu, Liming" uniqKey="Qu L" first="Liming" last="Qu">Liming Qu</name>
</region>
<name sortKey="Li, Mingyao" sort="Li, Mingyao" uniqKey="Li M" first="Mingyao" last="Li">Mingyao Li</name>
<name sortKey="Reilly, Muredach P" sort="Reilly, Muredach P" uniqKey="Reilly M" first="Muredach P." last="Reilly">Muredach P. Reilly</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Loley, Christina" sort="Loley, Christina" uniqKey="Loley C" first="Christina" last="Loley">Christina Loley</name>
</noRegion>
<name sortKey="Erdmann, Jeanette" sort="Erdmann, Jeanette" uniqKey="Erdmann J" first="Jeanette" last="Erdmann">Jeanette Erdmann</name>
<name sortKey="Hengstenberg, Christian" sort="Hengstenberg, Christian" uniqKey="Hengstenberg C" first="Christian" last="Hengstenberg">Christian Hengstenberg</name>
<name sortKey="Hengstenberg, Christian" sort="Hengstenberg, Christian" uniqKey="Hengstenberg C" first="Christian" last="Hengstenberg">Christian Hengstenberg</name>
<name sortKey="Konig, Inke R" sort="Konig, Inke R" uniqKey="Konig I" first="Inke R." last="König">Inke R. König</name>
<name sortKey="Schunkert, Heribert" sort="Schunkert, Heribert" uniqKey="Schunkert H" first="Heribert" last="Schunkert">Heribert Schunkert</name>
<name sortKey="Schunkert, Heribert" sort="Schunkert, Heribert" uniqKey="Schunkert H" first="Heribert" last="Schunkert">Heribert Schunkert</name>
</country>
<country name="Australie"><noRegion><name sortKey="Charchar, Fadi J" sort="Charchar, Fadi J" uniqKey="Charchar F" first="Fadi J." last="Charchar">Fadi J. Charchar</name>
</noRegion>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Arjo, Ares Rocanin" sort="Arjo, Ares Rocanin" uniqKey="Arjo A" first="Ares Rocanin" last="Arjo">Ares Rocanin Arjo</name>
</region>
<name sortKey="Arjo, Ares Rocanin" sort="Arjo, Ares Rocanin" uniqKey="Arjo A" first="Ares Rocanin" last="Arjo">Ares Rocanin Arjo</name>
<name sortKey="Arjo, Ares Rocanin" sort="Arjo, Ares Rocanin" uniqKey="Arjo A" first="Ares Rocanin" last="Arjo">Ares Rocanin Arjo</name>
<name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name>
<name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name>
<name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name>
<name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
<name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
<name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
</country>
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</affiliations>
</record>

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Serveur d'exploration sur les relations entre la France et l'Australie

Runs of Homozygosity: Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages

Runs of Homozygosity: Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages

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	Serveur d'exploration sur les relations entre la France et l'Australie
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