A Genetic Deconstruction of Neurocognitive Traits in Schizophrenia and Bipolar Disorder
Publication Date
December 12, 2013
Journal
PLOS ONE
Authors
Carla P. D. Fernandes, Andrea Christoforou, Sudheer Giddaluru, Kari M. Ersland, et al
Volume
8
Issue
12
Pages
e81052
DOI
https://dx.plos.org/10.1371/journal.pone.0081052
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0081052
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24349030
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861303
Europe PMC
http://europepmc.org/abstract/MED/24349030
Web of Science
000328731800010
Scopus
84892504753
Mendeley
http://www.mendeley.com/research/genetic-deconstruction-neurocognitive-traits-schizophrenia-bipolar-disorder
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Mendeley | Further Information

{"title"=>"A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar disorder", "type"=>"journal", "authors"=>[{"first_name"=>"Carla P.D.", "last_name"=>"Fernandes", "scopus_author_id"=>"55027036800"}, {"first_name"=>"Andrea", "last_name"=>"Christoforou", "scopus_author_id"=>"12800205100"}, {"first_name"=>"Sudheer", "last_name"=>"Giddaluru", "scopus_author_id"=>"36161938600"}, {"first_name"=>"Kari M.", "last_name"=>"Ersland", "scopus_author_id"=>"24175569500"}, {"first_name"=>"Srdjan", "last_name"=>"Djurovic", "scopus_author_id"=>"57189018625"}, {"first_name"=>"Manuel", "last_name"=>"Mattheisen", "scopus_author_id"=>"8636730800"}, {"first_name"=>"Astri J.", "last_name"=>"Lundervold", "scopus_author_id"=>"7004669019"}, {"first_name"=>"Ivar", "last_name"=>"Reinvang", "scopus_author_id"=>"7004098804"}, {"first_name"=>"Markus M.", "last_name"=>"Nöthen", "scopus_author_id"=>"35355123900"}, {"first_name"=>"Marcella", "last_name"=>"Rietschel", "scopus_author_id"=>"16741658400"}, {"first_name"=>"Roel A.", "last_name"=>"Ophoff", "scopus_author_id"=>"7004321340"}, {"first_name"=>"Albert", "last_name"=>"Hofman", "scopus_author_id"=>"36048731400"}, {"first_name"=>"André G.", "last_name"=>"Uitterlinden", "scopus_author_id"=>"35231615000"}, {"first_name"=>"Thomas", "last_name"=>"Werge", "scopus_author_id"=>"6701738296"}, {"first_name"=>"Sven", "last_name"=>"Cichon", "scopus_author_id"=>"56979466600"}, {"first_name"=>"Thomas", "last_name"=>"Espeseth", "scopus_author_id"=>"8596160700"}, {"first_name"=>"Ole A.", "last_name"=>"Andreassen", "scopus_author_id"=>"56600076200"}, {"first_name"=>"Vidar M.", "last_name"=>"Steen", "scopus_author_id"=>"7005011215"}, {"first_name"=>"Stephanie", "last_name"=>"Le Hellard", "scopus_author_id"=>"8612660600"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372141753", "sgr"=>"84892504753", "issn"=>"19326203", "pmid"=>"24349030", "scopus"=>"2-s2.0-84892504753", "doi"=>"10.1371/journal.pone.0081052", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"531142ae-31a8-338e-adc4-60b83326e09b", "abstract"=>"BACKGROUND: Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.\\n\\nMETHODS: Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium.\\n\\nRESULTS: The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope.\\n\\nCONCLUSIONS: Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.", "link"=>"http://www.mendeley.com/research/genetic-deconstruction-neurocognitive-traits-schizophrenia-bipolar-disorder", "reader_count"=>51, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>10, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>10, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>10, "Arts and Humanities"=>1, "Neuroscience"=>5, "Psychology"=>9, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Neuroscience"=>{"Neuroscience"=>5}, "Psychology"=>{"Psychology"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>5}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>1, "Germany"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1313998"], "description"=>"<p><sup></sup> BPD, bipolar disorder; SCZ, schizophrenia; NCNG, Norwegian Cognitive NeuroGenetics; TOP, Norwegian Thematically Organized Psychosis; WTCCC, British Wellcome Trust Case Control Consortium; Danish, Danish sub-sample of the Scandinavian Collaboration on Psychiatric Etiology; PGC, Psychiatric Genomics Consortium.</p><p><sup></sup> indicates the cases and controls in the single-centre samples that are also included in the PGC multi-centre sample.</p>", "links"=>[], "tags"=>[], "article_id"=>876904, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Carla P. D. Fernandes", "Andrea Christoforou", "Sudheer Giddaluru", "Kari M. Ersland", "Srdjan Djurovic", "Manuel Mattheisen", "Astri J. Lundervold", "Ivar Reinvang", "Markus M. Nöthen", "Marcella Rietschel", "Roel A. Ophoff", "Albert Hofman", "Andre G. Uitterlinden", "Thomas Werge", "Sven Cichon", "Thomas Espeseth", "Ole A. Andreassen", "Vidar M. Steen", "Stéphanie Le Hellard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081052.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_the_samples_/876904", "title"=>"Description of the samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-12 06:56:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313995"], "description"=>"<p>A1–A5: GWAS were performed for nine cognitive traits selected from the battery phenotyped in the healthy Norwegian NCNG sample (A1). Using the LDsnpR algorithm <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081052#pone.0081052-Christoforou1\" target=\"_blank\">[51]</a>, SNPs were assigned to gene bins (A2–3) and the gene bins were scored using the minimum <i>p</i>-value corrected for the number of SNPs in the bin with an adjusted Sidak <i>p</i>-value. The gene scores were ranked (smallest Sidak <i>p</i>-value to biggest – A4). These GWAS-based ranked lists of genes were used to generate the candidate gene sets, which comprised the top 25, 50, 100, 250, 500, 750, 1000, 1250, 1500, 1750 and 2000 genes associated with each of the cognitive traits (A5). Thus, the candidate gene sets were overlapping, and there was an incremental increase in the number of genes per set. B1–B4: The GWAS data for the psychiatric disorders (B1) were subjected to the same pipeline for assigning SNPs to gene bins (B2–3), scoring (see manuscript), and ranking the genes by their score (smallest Sidak <i>p</i>-value to the biggest – B4).</p>", "links"=>[], "tags"=>[], "article_id"=>876901, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Carla P. D. Fernandes", "Andrea Christoforou", "Sudheer Giddaluru", "Kari M. Ersland", "Srdjan Djurovic", "Manuel Mattheisen", "Astri J. Lundervold", "Ivar Reinvang", "Markus M. Nöthen", "Marcella Rietschel", "Roel A. Ophoff", "Albert Hofman", "Andre G. Uitterlinden", "Thomas Werge", "Sven Cichon", "Thomas Espeseth", "Ole A. Andreassen", "Vidar M. Steen", "Stéphanie Le Hellard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081052.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_representation_of_the_overall_method_/876901", "title"=>"Schematic representation of the overall method.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-12 06:56:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313996"], "description"=>"<p><i>q</i>-value, obtained from 3 GSEA runs with 1,000 permutations each). The maximum standard deviation from the average <i>q</i>-value was 0.07. Sets that passed the enrichment threshold (<i>p</i>-value≤0.05, FDR <i>q</i>-value≤0.25) were tested for validation using random mimic sets (see Table S4 in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081052#pone.0081052.s001\" target=\"_blank\">File S1</a>).<sup></sup> For each GWAS dataset, the 5 most enriched candidate sets are shown. For the German dataset, the 14 most enriched sets are presented to show the overlap with the other datasets. The rank position (R) of the gene set within the total number of gene sets tested is determined by the average false discovery rate (</p><p>% of the random sets (i.e. validated sets).<sup>a</sup> indicates sets that were more enriched than 98</p><p><sup>b</sup> indicates sets that did not pass the enrichment threshold but were among the 5 most enriched in the corresponding sample.</p><p>“n.e.”. Visuospatial attention.1 – Visuospatial attention task with valid cue to the location of the visual target; Visuospatial attention.3 – Visuospatial attention task with neutral cue to the location of the visual target. The number after each gene set name represents the number of genes within that set (e.g. the Colour-word interference −25 set contains the top 25 genes within the colour-word interference ranking list of genes).<sup></sup> Sets that did not pass the enrichment threshold and ranked outside the top 5 are indicated by </p><p><i>p-</i>value of zero (0.0) indicates an actual <i>p</i>-value of less than 1/number-of-permutations.<sup></sup> A reported </p>", "links"=>[], "tags"=>["sets", "neurocognitive", "enrichment", "bipolar"], "article_id"=>876902, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Carla P. D. Fernandes", "Andrea Christoforou", "Sudheer Giddaluru", "Kari M. Ersland", "Srdjan Djurovic", "Manuel Mattheisen", "Astri J. Lundervold", "Ivar Reinvang", "Markus M. Nöthen", "Marcella Rietschel", "Roel A. Ophoff", "Albert Hofman", "Andre G. Uitterlinden", "Thomas Werge", "Sven Cichon", "Thomas Espeseth", "Ole A. Andreassen", "Vidar M. Steen", "Stéphanie Le Hellard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081052.t002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Testing_gene_sets_associated_with_normal_neurocognitive_variation_for_enrichment_of_association_with_bipolar_disorder_/876902", "title"=>"Testing gene sets associated with normal neurocognitive variation for enrichment of association with bipolar disorder.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-12 06:56:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313999"], "description"=>"<div><p>Background</p><p>Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.</p><p>Methods</p><p>Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium.</p><p>Results</p><p>The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope.</p><p>Conclusions</p><p>Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.</p></div>", "links"=>[], "tags"=>["deconstruction", "neurocognitive", "schizophrenia", "bipolar"], "article_id"=>876905, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Carla P. D. Fernandes", "Andrea Christoforou", "Sudheer Giddaluru", "Kari M. Ersland", "Srdjan Djurovic", "Manuel Mattheisen", "Astri J. Lundervold", "Ivar Reinvang", "Markus M. Nöthen", "Marcella Rietschel", "Roel A. Ophoff", "Albert Hofman", "Andre G. Uitterlinden", "Thomas Werge", "Sven Cichon", "Thomas Espeseth", "Ole A. Andreassen", "Vidar M. Steen", "Stéphanie Le Hellard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081052", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Genetic_Deconstruction_of_Neurocognitive_Traits_in_Schizophrenia_and_Bipolar_Disorder_/876905", "title"=>"A Genetic Deconstruction of Neurocognitive Traits in Schizophrenia and Bipolar Disorder", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-12 06:56:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313997"], "description"=>"<p><i>q</i>-value, obtained from 3 GSEA runs with 1,000 permutations each). The maximum standard deviation from the average <i>q</i>-value was 0.06. Sets that passed the enrichment threshold (<i>p</i>-value≤0.05, FDR <i>q</i>-value≤0.25) were tested for validation using random mimic sets (see Table S4 in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081052#pone.0081052.s001\" target=\"_blank\">File S1</a>).<sup></sup> For each GWAS dataset the 5 most enriched candidate sets are shown. The rank position (R) of the gene set within the total number of gene sets tested was determined by the average false discovery rate (</p><p>% of the random sets (i.e. validated sets).<sup>a</sup> indicates sets that were more enriched than 98</p><p><sup>b</sup> indicates sets that did not pass the enrichment threshold but were among the 5 most enriched in the corresponding sample.</p><p>“n.e.”. Visuospatial attention.1 – Visuospatial attention task with valid cue to the location of the visual target; Visuospatial attention.3 – Visuospatial attention task with neutral cue to the location of the visual target. The number after each gene set name represents the number of genes within that set (e.g. the Colour-word interference −25 set contains the top 25 genes within the colour-word interference ranking list of genes).<sup></sup> Sets that did not pass the enrichment threshold and ranked outside the top 5 are indicated by </p>", "links"=>[], "tags"=>["sets", "neurocognitive", "enrichment"], "article_id"=>876903, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Carla P. D. Fernandes", "Andrea Christoforou", "Sudheer Giddaluru", "Kari M. Ersland", "Srdjan Djurovic", "Manuel Mattheisen", "Astri J. Lundervold", "Ivar Reinvang", "Markus M. Nöthen", "Marcella Rietschel", "Roel A. Ophoff", "Albert Hofman", "Andre G. Uitterlinden", "Thomas Werge", "Sven Cichon", "Thomas Espeseth", "Ole A. Andreassen", "Vidar M. Steen", "Stéphanie Le Hellard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0081052.t003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Testing_gene_sets_associated_with_normal_neurocognitive_variation_for_enrichment_of_association_with_schizophrenia_/876903", "title"=>"Testing gene sets associated with normal neurocognitive variation for enrichment of association with schizophrenia.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-12 06:56:32"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Computational biology", "average_usage"=>[295, 511, 651, 775, 882, 992, 1100, 1201, 1304, 1400, 1486, 1570, 1650]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/Medicine and health sciences/Mental health and psychiatry", "average_usage"=>[282, 468, 596, 706, 804, 895, 1000, 1081, 1175, 1272, 1356, 1445, 1531]}, {"subject_area"=>"/Social sciences", "average_usage"=>[289, 475, 593, 703, 805, 902, 990, 1078, 1158, 1250, 1336, 1417, 1482]}, {"subject_area"=>"/Social sciences/Psychology", "average_usage"=>[294, 460, 580, 683, 777, 868, 957, 1044, 1124, 1202, 1276, 1356, 1422]}]}
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