Combined Effects of Thrombosis Pathway Gene Variants Predict Cardiovascular Events
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{"title"=>"Combined effects of thrombosis pathway gene variants predict cardiovascular events", "type"=>"journal", "authors"=>[{"first_name"=>"Kirsi", "last_name"=>"Auro", "scopus_author_id"=>"13613860800"}, {"first_name"=>"Mervi", "last_name"=>"Alanne", "scopus_author_id"=>"8541855200"}, {"first_name"=>"Kati", "last_name"=>"Kristiansson", "scopus_author_id"=>"18234154400"}, {"first_name"=>"Kaisa", "last_name"=>"Silander", "scopus_author_id"=>"6603017528"}, {"first_name"=>"Kari", "last_name"=>"Kuulasmaa", "scopus_author_id"=>"7004232837"}, {"first_name"=>"Veikko", "last_name"=>"Salomaa", "scopus_author_id"=>"7004714461"}, {"first_name"=>"Leena", "last_name"=>"Peltonen", "scopus_author_id"=>"36051313500"}, {"first_name"=>"Markus", "last_name"=>"Perola", "scopus_author_id"=>"7003719630"}], "year"=>2007, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"17677000", "doi"=>"10.1371/journal.pgen.0030120", "sgr"=>"34547637926", "isbn"=>"1553-7390\\r1553-7404", "scopus"=>"2-s2.0-34547637926", "issn"=>"15537390", "pui"=>"47203974"}, "id"=>"5502af10-fdae-3669-ac2b-284146ded1e6", "abstract"=>"The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellular adhesion molecule 1 (ICAM1), protein C (PROC), and thrombomodulin (THBD) in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, n = 5,999 and FINRISK-97, n = 8,141), we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD) cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%), 54 single nucleotide polymorphisms (SNPs) were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of F5 rs7542281 x THBD rs1042580, together with three single F5 SNPs, was associated with CVD events. Among men, PROC rs1041296, when combined with either ICAM1 rs5030341 or F5 rs2269648, was associated with total mortality. As a single variant, PROC rs1401296, together with the F5 Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs-acting either in combination or as single variants--predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level.", "link"=>"http://www.mendeley.com/research/combined-effects-thrombosis-pathway-gene-variants-predict-cardiovascular-events-3", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>3, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>3, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>3, "Arts and Humanities"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Colombia"=>1, "Netherlands"=>1, "Germany"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/947145"], "description"=>"<p>SNPs are analyzed as 0 (minor allele carriers) to 1 (major allele homozygotes), modeling dominant inheritance.</p>", "links"=>[], "tags"=>["classification-tree", "subsample", "consisting"], "article_id"=>617489, "categories"=>["Medicine", "Genetics"], "users"=>["Kirsi Auro", "Mervi Alanne", "Kati Kristiansson", "Kaisa Silander", "Kari Kuulasmaa", "Veikko Salomaa", "Leena Peltonen", "Markus Perola"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0030120.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Example_of_a_Classification_Tree_in_a_Random_Female_Subsample_Consisting_of_60_of_the_Original_Data_/617489", "title"=>"Example of a Classification-Tree in a Random Female Subsample Consisting of 60% of the Original Data", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-07-27 02:04:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/947308"], "description"=>"<p>Schematic Overview of the Interplay of Traditional Cardiovascular Risk Factors and Genetic Variants Contributing to Disease Risk in Our Study Sample</p>", "links"=>[], "tags"=>["overview", "interplay", "cardiovascular", "variants", "contributing"], "article_id"=>617643, "categories"=>["Medicine", "Genetics"], "users"=>["Kirsi Auro", "Mervi Alanne", "Kati Kristiansson", "Kaisa Silander", "Kari Kuulasmaa", "Veikko Salomaa", "Leena Peltonen", "Markus Perola"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0030120.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_Overview_of_the_Interplay_of_Traditional_Cardiovascular_Risk_Factors_and_Genetic_Variants_Contributing_to_Disease_Risk_in_Our_Study_Sample_/617643", "title"=>"Schematic Overview of the Interplay of Traditional Cardiovascular Risk Factors and Genetic Variants Contributing to Disease Risk in Our Study Sample", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-07-27 02:07:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/466695", "https://ndownloader.figshare.com/files/466728", "https://ndownloader.figshare.com/files/466832", "https://ndownloader.figshare.com/files/466953", "https://ndownloader.figshare.com/files/467053", "https://ndownloader.figshare.com/files/467153", "https://ndownloader.figshare.com/files/467258", "https://ndownloader.figshare.com/files/467382", "https://ndownloader.figshare.com/files/467472", "https://ndownloader.figshare.com/files/467578", "https://ndownloader.figshare.com/files/467689", "https://ndownloader.figshare.com/files/467793", "https://ndownloader.figshare.com/files/467904", "https://ndownloader.figshare.com/files/468035", "https://ndownloader.figshare.com/files/468146", "https://ndownloader.figshare.com/files/468224", "https://ndownloader.figshare.com/files/468327"], "description"=>"<div><p>The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V <em>(F5),</em> intercellular adhesion molecule 1 <em>(ICAM1),</em> protein C <em>(PROC),</em> and thrombomodulin <em>(THBD)</em> in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, <em>n</em> = 5,999 and FINRISK-97, <em>n</em> = 8,141), we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD) cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%), 54 single nucleotide polymorphisms (SNPs) were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of <em>F5 rs7542281</em> × <em>THBD rs1042580,</em> together with three single <em>F5</em> SNPs, was associated with CVD events. Among men, <em>PROC rs1041296,</em> when combined with either <em>ICAM1 rs5030341</em> or <em>F5 rs2269648,</em> was associated with total mortality. As a single variant, <em>PROC rs1401296,</em> together with the <em>F5</em> Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs—acting either in combination or as single variants—predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level.</p></div>", "links"=>[], "tags"=>["effects", "thrombosis", "pathway", "variants", "cardiovascular", "events"], "article_id"=>151997, "categories"=>["Medicine", "Genetics"], "users"=>["Kirsi Auro", "Mervi Alanne", "Kati Kristiansson", "Kaisa Silander", "Kari Kuulasmaa", "Veikko Salomaa", "Leena Peltonen", "Markus Perola"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0030120.sg001", "https://dx.doi.org/10.1371/journal.pgen.0030120.st001", "https://dx.doi.org/10.1371/journal.pgen.0030120.st002", "https://dx.doi.org/10.1371/journal.pgen.0030120.st003", "https://dx.doi.org/10.1371/journal.pgen.0030120.st004", "https://dx.doi.org/10.1371/journal.pgen.0030120.st005", "https://dx.doi.org/10.1371/journal.pgen.0030120.st006", "https://dx.doi.org/10.1371/journal.pgen.0030120.st007", "https://dx.doi.org/10.1371/journal.pgen.0030120.st008", "https://dx.doi.org/10.1371/journal.pgen.0030120.st009", "https://dx.doi.org/10.1371/journal.pgen.0030120.st010", "https://dx.doi.org/10.1371/journal.pgen.0030120.st011", "https://dx.doi.org/10.1371/journal.pgen.0030120.st012", "https://dx.doi.org/10.1371/journal.pgen.0030120.st013", "https://dx.doi.org/10.1371/journal.pgen.0030120.st014", "https://dx.doi.org/10.1371/journal.pgen.0030120.st015", "https://dx.doi.org/10.1371/journal.pgen.0030120.st016"], "stats"=>{"downloads"=>24, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Combined_Effects_of_Thrombosis_Pathway_Gene_Variants_Predict_Cardiovascular_Events/151997", "title"=>"Combined Effects of Thrombosis Pathway Gene Variants Predict Cardiovascular Events", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-07-27 00:33:17"}

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  • {"unique-ip"=>"7", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"15", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

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