Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder

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.

• Autores: Gómez Makhinson, Juliana; López Tobón, María Cecilia; Montoya Montoya, Gabriel; Montoya Guerra, Claudia Patricia; Ospina Duque, Jorge; López Jaramillo, Carlos Alberto; Pagani, Lucia; Clair, Patricia; Teshiba, Terri; Service, Susan; Fears, Scott; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramírez, Margarita; Castrillón, Gabriel; Aldana, Ileana; Navarro, Linda; Freimer, Daniel; Safaie, Brian; Keung, Lap Woon; Greenspan, Kiefer; Chou, Katty; Escobar, Javier; Kremeyer, Barbara; Ruiz Linares, Andrés; Cantor, Rita; Macaya, Gabriel; Molina, Julio; Reus, Victor; Sabatti, Chiara; Bearden, Carrie; Takahashi, Joseph; Freimer, Nelson
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2015
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/19266
• Acceso en línea: http://hdl.handle.net/10495/19266
• Palabra clave: Trastorno Bipolar; Bipolar disorder; Endofenotipos; Endophenotypes; Ritmo Circadiano; Circadian rhythms; Actigrafía; Actigraphy; Conducta; Behavior
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/