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

Lucia Pagani, Patricia A St Clair, Terri M. Teshiba, Susan K. Service, Scott C. Fears, Carmen Araya, Xinia Araya, Julio Bejarano, Margarita Ramirez, Gabriel Castrillón, Juliana Gomez-Makhinson, Maria C. Lopez, Gabriel Montoya, Claudia P. Montoya, Ileana Aldana, Linda Navarro, Daniel G. Freimer, Brian Safaie, Lap Woon Keung, Kiefer GreenspanKatty Chou, Javier I. Escobar, Jorge Ospina-Duque, Barbara Kremeyer, Andres Ruiz-Linares, Rita M. Cantor, Carlos Lopez-Jaramillo, Gabriel Macaya, Julio Molina, Victor I. Reus, Chiara Sabatti, Carrie E. Bearden, Joseph S. Takahashi, Nelson B. Freimer

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)E754-E761
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number6
DOIs
StatePublished - Feb 9 2016

Fingerprint

Pedigree
Circadian Rhythm
Bipolar Disorder
Sleep
Phenotype
Actigraphy
Genetic Linkage
Chromosomes
Genome

Keywords

  • Actigraphy
  • Behavior
  • Bipolar disorder
  • Circadian rhythms
  • Endophenotypes

ASJC Scopus subject areas

  • General

Cite this

Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder. / Pagani, Lucia; Clair, Patricia A St; 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 6, 09.02.2016, p. E754-E761.

Research output: Contribution to journalArticle

Pagani, L, Clair, PAS, Teshiba, TM, Service, SK, Fears, SC, Araya, C, Araya, X, Bejarano, J, Ramirez, M, Castrillón, G, Gomez-Makhinson, J, Lopez, MC, Montoya, G, Montoya, CP, Aldana, I, Navarro, L, Freimer, DG, Safaie, B, Keung, LW, Greenspan, K, Chou, K, Escobar, JI, Ospina-Duque, J, Kremeyer, B, Ruiz-Linares, A, Cantor, RM, Lopez-Jaramillo, C, Macaya, G, Molina, J, Reus, VI, Sabatti, C, Bearden, CE, Takahashi, JS & Freimer, NB 2016, 'Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 6, pp. E754-E761. https://doi.org/10.1073/pnas.1513525113
Pagani, Lucia ; Clair, Patricia A St ; 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. / Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 6. pp. E754-E761.
@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.}",
year = "2016",
month = "2",
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",
number = "6",

}

TY - JOUR

T1 - Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder

AU - Pagani, Lucia

AU - Clair, Patricia A St

AU - Teshiba, Terri M.

AU - Service, Susan K.

AU - Fears, Scott C.

AU - Araya, Carmen

AU - Araya, Xinia

AU - Bejarano, Julio

AU - Ramirez, Margarita

AU - Castrillón, Gabriel

AU - Gomez-Makhinson, Juliana

AU - Lopez, Maria C.

AU - Montoya, Gabriel

AU - Montoya, Claudia P.

AU - Aldana, Ileana

AU - Navarro, Linda

AU - Freimer, Daniel G.

AU - Safaie, Brian

AU - Keung, Lap Woon

AU - Greenspan, Kiefer

AU - Chou, Katty

AU - Escobar, Javier I.

AU - Ospina-Duque, Jorge

AU - Kremeyer, Barbara

AU - Ruiz-Linares, Andres

AU - Cantor, Rita M.

AU - Lopez-Jaramillo, Carlos

AU - Macaya, Gabriel

AU - Molina, Julio

AU - Reus, Victor I.

AU - Sabatti, Chiara

AU - Bearden, Carrie E.

AU - Takahashi, Joseph S.

AU - Freimer, Nelson B.

PY - 2016/2/9

Y1 - 2016/2/9

N2 - 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.

AB - 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.

KW - Actigraphy

KW - Behavior

KW - Bipolar disorder

KW - Circadian rhythms

KW - Endophenotypes

UR - http://www.scopus.com/inward/record.url?scp=84957824634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957824634&partnerID=8YFLogxK

U2 - 10.1073/pnas.1513525113

DO - 10.1073/pnas.1513525113

M3 - Article

C2 - 26712028

AN - SCOPUS:84957824634

VL - 113

SP - E754-E761

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 6

ER -