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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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 113; H. 6; S. E754
Hauptverfasser: Pagani, Lucia, St Clair, Patricia A, Teshiba, Terri M, Service, Susan K, Fears, Scott C, Araya, Carmen, Araya, Xinia, Bejarano, Julio, Ramirez, Margarita, Castrillón, Gabriel, Gomez-Makhinson, Juliana, Lopez, Maria C, Montoya, Gabriel, Montoya, Claudia P, Aldana, Ileana, Navarro, Linda, Freimer, Daniel G, Safaie, Brian, Keung, Lap-Woon, Greenspan, Kiefer, Chou, Katty, Escobar, Javier I, Ospina-Duque, Jorge, Kremeyer, Barbara, Ruiz-Linares, Andres, Cantor, Rita M, Lopez-Jaramillo, Carlos, Macaya, Gabriel, Molina, Julio, Reus, Victor I, Sabatti, Chiara, Bearden, Carrie E, Takahashi, Joseph S, Freimer, Nelson B
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 09.02.2016
Schlagworte:
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
bipolar disorder
actigraphy
behavior
circadian rhythms
endophenotypes
ISSN:1091-6490, 1091-6490
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1513525113