Multisystem Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

Fears, Scott C.; Kremeyer, Bárbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Mark; Castrillón, Gabriel; Gomez-Franco, Juliana; López, María Cecilia; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri; Abaryan, Zvart; Al‐Sharif, Noor; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori L.; Bartzokis, George; Escobar, Javier I.; Glahn, David C.; Ospina‐Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; López‐Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

doi:10.1001/jamapsychiatry.2013.4100

Cited by 115 publications

(106 citation statements)

References 111 publications

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“…founder populations are likely to show increased frequencies for many deleterious alleles-another feature that will enhance their utility for mapping these traits (10,11). We previously described, in these pedigrees, multiple heritable and BP-associated phenotypes from the domains of temperament, neurocognition, and neuroanatomy (10).…”

Section: Significancementioning

confidence: 99%

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

Pagani

Clair

Teshiba

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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. bipolar disorder | endophenotypes | circadian rhythms | actigraphy | behavior Q uantitative sleep and activity measures are hypothesized to be endophenotypes for bipolar disorder (BP). Disturbance of sleep and circadian activity typically precedes and may precipitate the initial onset of BP (1, 2). Decreased sleep and increased activity occur before and during manic and hypomanic episodes. Conversely, increased sleep and decreased activity characterize BP-depression. Extreme diurnal variation in mood features prominently in both mania and depression, whereas shifts in circadian phase (the time within the daily activity cycle at which periodic phenomena such as bed time or awakening occur) can induce mania and ameliorate symptoms of BP-depression (3).Twin studies have identified multiple heritable sleep and activity phenotypes, including sleep duration, sleep quality, phase of activity preference and sleep pattern, and sleep architecture variables [e.g., the amount of slow wave and rapid eye movement (REM) sleep (4) and polysomnography profiles during non-REM sleep (5)]. Euthymic BP individuals, compared with healthy controls, display trait-like alterations in several such phenotypesfor example, sleep time and time in bed, sleep onset latency, and periods of being awake after sleep onset (6). However, no prior investigations have assayed the heritability of such phenotypes in BP individuals and their relatives.We report here the delineation of sleep and activity BP endophenotypes through investigations of 26 pedigrees (n = 558) ascertained for severe BP (BP-I), from the genetically related populations of the Central Valley of Costa Rica (CR) and Antioquia, Colombia (CO) (7-9). Pedigrees ascertained for multiple cases of severe BP (BP-I) should be enriched for extreme values of quantitative traits that are BP endophenotypes, enhancing their utility for genetic mapping studies of such phenotypes. Additionally, su...

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Section: Significancementioning

confidence: 99%

“…We previously described, in these pedigrees, multiple heritable and BP-associated phenotypes from the domains of temperament, neurocognition, and neuroanatomy (10).…”

Section: Significancementioning

confidence: 99%

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

Pagani

Clair

Teshiba

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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show abstract

“…An international collaborative team, which included clinicians and scientists from Costa Rica and Colombia, embarked on an ambitious project to measure a wide range of quantitative traits in euthymic BP subjects and their non-BP family members. In addition to clinical assessments, and measurements of sleep, activity, and circadian rhythms (4), they also assessed the familial aggregation of 169 traits from neurocognitive batteries and neuroimaging (9,10).…”

mentioning

confidence: 99%

“…Using sophisticated statistical methodology, Fears et al (9) identified 126 significantly heritable and 53 were associated with severe BP (BP-I). Among phenotypes that are heritable and associated with BP are proneness to delusions, perceptual creativity, and Fig.…”

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Expanding the phenotype half of the genotype−phenotype space

Bućan

2016

Proc. Natl. Acad. Sci. U.S.A.

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Errors in Identification of 17 of 527 Brain Images in Genetic Study of Phenotypes Associated With Bipolar Disorder

Fears

Bearden

2016

JAMA Psychiatry

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Multisystem Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

Cited by 115 publications

References 111 publications

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

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

Expanding the phenotype half of the genotype−phenotype space

Errors in Identification of 17 of 527 Brain Images in Genetic Study of Phenotypes Associated With Bipolar Disorder

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