Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder
Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 6; p. E754 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
09.02.2016
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| ISSN: | 1091-6490, 1091-6490 |
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| Abstract | Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes. |
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| AbstractList | Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes. Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes. |
| Author | Gomez-Makhinson, Juliana Reus, Victor I Sabatti, Chiara Araya, Carmen Montoya, Gabriel Chou, Katty Bejarano, Julio Freimer, Nelson B Montoya, Claudia P Navarro, Linda Bearden, Carrie E Araya, Xinia Aldana, Ileana Kremeyer, Barbara Cantor, Rita M Keung, Lap-Woon Greenspan, Kiefer Ruiz-Linares, Andres Escobar, Javier I Molina, Julio St Clair, Patricia A Service, Susan K Lopez, Maria C Takahashi, Joseph S Ramirez, Margarita Fears, Scott C Safaie, Brian Lopez-Jaramillo, Carlos Freimer, Daniel G Ospina-Duque, Jorge Macaya, Gabriel Castrillón, Gabriel Pagani, Lucia Teshiba, Terri M |
| Author_xml | – sequence: 1 givenname: Lucia surname: Pagani fullname: Pagani, Lucia organization: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390 – sequence: 2 givenname: Patricia A surname: St Clair fullname: St Clair, Patricia A organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 3 givenname: Terri M surname: Teshiba fullname: Teshiba, Terri M organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 4 givenname: Susan K surname: Service fullname: Service, Susan K organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 5 givenname: Scott C surname: Fears fullname: Fears, Scott C organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 6 givenname: Carmen surname: Araya fullname: Araya, Carmen organization: Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica 11501 – sequence: 7 givenname: Xinia surname: Araya fullname: Araya, Xinia organization: Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica 11501 – sequence: 8 givenname: Julio surname: Bejarano fullname: Bejarano, Julio organization: Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica 11501 – sequence: 9 givenname: Margarita surname: Ramirez fullname: Ramirez, Margarita organization: Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica 11501 – sequence: 10 givenname: Gabriel surname: Castrillón fullname: Castrillón, Gabriel organization: Instituto de Alta Tecnología Médica de Antioquia, Medellín, Colombia 050026 – sequence: 11 givenname: Juliana surname: Gomez-Makhinson fullname: Gomez-Makhinson, Juliana organization: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 050011 – sequence: 12 givenname: Maria C surname: Lopez fullname: Lopez, Maria C organization: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 050011 – sequence: 13 givenname: Gabriel surname: Montoya fullname: Montoya, Gabriel organization: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 050011 – sequence: 14 givenname: Claudia P surname: Montoya fullname: Montoya, Claudia P organization: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 050011 – sequence: 15 givenname: Ileana surname: Aldana fullname: Aldana, Ileana organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 16 givenname: Linda surname: Navarro fullname: Navarro, Linda organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 17 givenname: Daniel G surname: Freimer fullname: Freimer, Daniel G organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 18 givenname: Brian surname: Safaie fullname: Safaie, Brian organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 19 givenname: Lap-Woon surname: Keung fullname: Keung, Lap-Woon organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 20 givenname: Kiefer surname: Greenspan fullname: Greenspan, Kiefer organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 21 givenname: Katty surname: Chou fullname: Chou, Katty organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 22 givenname: Javier I surname: Escobar fullname: Escobar, Javier I organization: Department of Psychiatry and Family Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901 – sequence: 23 givenname: Jorge surname: Ospina-Duque fullname: Ospina-Duque, Jorge organization: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 050011 – sequence: 24 givenname: Barbara surname: Kremeyer fullname: Kremeyer, Barbara organization: Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom – sequence: 25 givenname: Andres surname: Ruiz-Linares fullname: Ruiz-Linares, Andres organization: Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom – sequence: 26 givenname: Rita M surname: Cantor fullname: Cantor, Rita M organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 27 givenname: Carlos surname: Lopez-Jaramillo fullname: Lopez-Jaramillo, Carlos organization: Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Departamento de Psiquiatría Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 050011; Mood Disorders Program, Hospital San Vicente Fundacion, Medellín, Colombia 050011 – sequence: 28 givenname: Gabriel surname: Macaya fullname: Macaya, Gabriel organization: Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, San José, Costa Rica 11501 – sequence: 29 givenname: Julio surname: Molina fullname: Molina, Julio organization: BioCiencias Lab, 01010 Guatemala, Guatemala – sequence: 30 givenname: Victor I surname: Reus fullname: Reus, Victor I organization: Department of Psychiatry, University of California, San Francisco, CA 94143 – sequence: 31 givenname: Chiara surname: Sabatti fullname: Sabatti, Chiara organization: Department of Health Research and Policy, Division of Biostatistics, Stanford University, Stanford, CA 94305 – sequence: 32 givenname: Carrie E surname: Bearden fullname: Bearden, Carrie E organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 – sequence: 33 givenname: Joseph S surname: Takahashi fullname: Takahashi, Joseph S email: joseph.takahashi@utsouthwestern.edu, nfreimer@mednet.ucla.edu organization: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 joseph.takahashi@utsouthwestern.edu nfreimer@mednet.ucla.edu – sequence: 34 givenname: Nelson B surname: Freimer fullname: Freimer, Nelson B email: joseph.takahashi@utsouthwestern.edu, nfreimer@mednet.ucla.edu organization: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095; joseph.takahashi@utsouthwestern.edu nfreimer@mednet.ucla.edu |
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| Snippet | Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our... |
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| SubjectTerms | Actigraphy Bipolar Disorder - genetics Bipolar Disorder - physiopathology Chromosomes, Human, Pair 1 - genetics Circadian Rhythm Family Female Humans Inheritance Patterns - genetics Lod Score Male Middle Aged Pedigree Phenotype Quantitative Trait, Heritable Sleep |
| Title | Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder |
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