@article{2aa168e4ac084c7086d5ebf29ea4a893,
title = "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.",
keywords = "Actigraphy, Behavior, Bipolar disorder, Circadian rhythms, Endophenotypes",
author = "Lucia Pagani and Clair, {Patricia A St} and Teshiba, {Terri M.} and Service, {Susan K.} and Fears, {Scott C.} and Carmen Araya and Xinia Araya and Julio Bejarano and Margarita Ramirez and Gabriel Castrill{\'o}n and Juliana Gomez-Makhinson and Lopez, {Maria C.} and Gabriel Montoya and Montoya, {Claudia P.} and Ileana Aldana and Linda Navarro and Freimer, {Daniel G.} and Brian Safaie and Keung, {Lap Woon} and Kiefer Greenspan and Katty Chou and Escobar, {Javier I.} and Jorge Ospina-Duque and Barbara Kremeyer and Andres Ruiz-Linares and Cantor, {Rita M.} and Carlos Lopez-Jaramillo and Gabriel Macaya and Julio Molina and Reus, {Victor I.} and Chiara Sabatti and Bearden, {Carrie E.} and Takahashi, {Joseph S.} and Freimer, {Nelson B.}",
note = "Funding Information: We thank the members of CR and CO families for participating in this study and John Blangero and Thomas Dyer (Texas Biomedical Research Institute and University of Texas Health Science Center) for calculating MIBDs. This research was supported by National Institute of Health Grants R01MH075007, R01MH095454, and P30NS062691 (to N.B.F.), T32MH073526 (to P.A.S.C.), K23MH074644-01 (to C.E.B.), and K08MH086786 (to S.C.F.), the Colciencias and Codi-University of Antioquia (to C.L.-J.), and the Joanne and George Miller Family Endowed Term Chair (to C.E.B.). J.S.T. is an investigator in the Howard Hughes Medical Institute.",
year = "2016",
month = feb,
day = "9",
doi = "10.1073/pnas.1513525113",
language = "English (US)",
volume = "113",
pages = "E754--E761",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "6",
}