Evidence map›Paper›PMID 24522887›Full record

ArticleJAMA psychiatry2014

Multisystem component phenotypes of bipolar disorder for genetic investigations of extended pedigrees.

Scott C Fears, Susan K Service, Barbara Kremeyer, Carmen Araya, Xinia Araya, Julio Bejarano, Margarita Ramirez, Gabriel Castrillón, Juliana Gomez-Franco, Maria C Lopez and 27 more

Erratum issuedAbstract read
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In one paragraph

Article in JAMA psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. The genetics of bipolar disorder.Molecular psychiatry · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. The Emerging Neurobiology of Bipolar Disorder.Trends in neurosciences · 2018
    Review
  17. Article
  18. Review
  19. So Where Are the Genes for Bipolar Disorder?Focus (American Psychiatric Publishing) · 2017
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors.

Scott C FearsDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Susan K ServiceDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Barbara KremeyerWellcome Trust Sanger Institute, Hinxton, England.
Carmen ArayaCell and Molecular Biology Research, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica.
Xinia ArayaCell and Molecular Biology Research, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica.
Julio BejaranoCell and Molecular Biology Research, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica.
Margarita RamirezCell and Molecular Biology Research, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica.
Gabriel CastrillónInstituto de Alta Tecnología Médica de Antioquia, Medellín, Colombia.
Juliana Gomez-FrancoGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Maria C LopezGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Gabriel MontoyaGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Patricia MontoyaGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Ileana AldanaDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Terri M TeshibaDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Zvart AbaryanDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Noor B Al-SharifDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Marissa EricsonDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Maria JalbrzikowskiDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Jurjen J LuykxDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles6Department of Psychiatry, ZNA Stuivenberg, Antwerp, Belgium.
Linda NavarroDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Todd A TishlerDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Lori AltshulerDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
George BartzokisDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Javier EscobarDepartment of Psychiatry and Family Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick.
David C GlahnDepartment of Psychiatry, Yale University, New Haven, Connecticut9Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut.
Jorge Ospina-DuqueGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Neil RischInstitute for Human Genetics, University of California, San Francisco.
Andrés Ruiz-LinaresDepartment of Genetics, Evolution, and Environment, University College London, London, England.
Paul M ThompsonDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Rita M CantorDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Carlos Lopez-JaramilloGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia12Mood Disorders Program, Hospital San Vicente Fundacion, Medellín, Colombia.
Gabriel MacayaCell and Molecular Biology Research, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica.
Julio MolinaDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles13BioCiencias Lab, Guatemala, Guatemala.
Victor I ReusDepartment of Psychiatry, University of California, San Francisco.
Chiara SabattiDepartment of Health Research and Policy, Stanford University, Stanford, California.
Nelson B FreimerDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Carrie E BeardenDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.

Funding

Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4M
Genetics of Severe Mental IllnessR01MH113078 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, FREIMER, NELSON B. · 2017 to 2021
$5.8M
Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
Bipolar Endophenotypes in Population IsolatesR01MH075007 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2007 to 2011
$3.8M
Genome Sequencing in Extended Bipolar PedigreesR01MH095454 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2012 to 2014
$2.4M
New Statistical Methods for High Resolution Mapping of Multiple PhenotypesR01HG006695 · NHGRI · STANFORD UNIVERSITY · PI SABATTI, CHIARA · 2013 to 2015
$1.0M
Quantitative Genetic Analyisis of Brain Structural PhenotypesK08MH086786 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FEARS, SCOTT C. · 2009 to 2013
$925k
Identification of endophenotypes for bipolar disorderK23MH074644 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E · 2005 to 2009
$808k
NHGRI NIH HHS R01 HG006695NHGRI NIH HHS R01HG006695NIMH NIH HHS K08 MH086786NIMH NIH HHS K08MH086786NIMH NIH HHS K23 MH074644NIMH NIH HHS K23MH074644-01NIMH NIH HHS R01 MH075007NIMH NIH HHS R01MH075007NIMH NIH HHS R01 MH095454NIMH NIH HHS R01MH095454NIMH NIH HHS R01 MH113078NINDS NIH HHS P30 NS062691NINDS NIH HHS P30NS062691NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

importanceGenetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes.

objectiveTo identify quantitative neurocognitive, temperament-related, and neuroanatomical phenotypes that appear heritable and associated with severe BP (bipolar I disorder [BP-I]) and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN, SETTING, AND

participantsMultigenerational pedigree study in 2 closely related, genetically isolated populations: the Central Valley of Costa Rica and Antioquia, Colombia. A total of 738 individuals, all from Central Valley of Costa Rica and Antioquia pedigrees, participated; among them, 181 have BP-I. MAIN OUTCOMES AND MEASURES: Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging, and diffusion tensor imaging phenotypes.

resultsOf 169 phenotypes investigated, 126 (75%) were significantly heritable and 53 (31%) were associated with BP-I. About one-quarter of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions as well as volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I association within families that is consistent with expectations from case-control studies. Together, these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder.

Indexed as

PhenotypeAdultBipolar DisorderBrainCerebral CortexFemaleGenetic LinkageGenetic Predisposition to DiseaseHumansMagnetic Resonance ImagingMaleNeuropsychological TestsOrgan SizePedigreeStatistics as TopicTemperament

Identifiers

PMID24522887
PMCPMC4045237

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.