A common polymorphism near PER1 and the timing of human behavioral rhythms

Andrew S P Lim, Anne Marie Chang, Joshua M. Shulman, Towfique Raj, Lori B. Chibnik, Sean W. Cain, Katherine Rothamel, Christophe Benoist, Amanda J Myers, Charles A. Czeisler, Aron S. Buchman, David A. Bennett, Jeanne F. Duffy, Clifford B. Saper, Philip L. De Jager

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective: Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self-reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level. Methods: We performed a candidate gene association study with replication, evaluating associations between polymorphisms in homologs of evolutionarily conserved clock genes and the timing of behavioral rhythms measured by actigraphy. For validated polymorphisms, we evaluated associations with transcript expression and time of death in additional cohorts. Results: rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms in both the discovery and replication cohorts (joint p = 2.1 × 10-7). Mean activity timing was delayed by 67 minutes in rs7221412GG versus rs7221412AA homozygotes. rs7221412 also showed a suggestive time-dependent relationship with both cerebral cortex (p = 0.05) and CD14+CD16- monocyte (p = 0.02) PER1 expression and an interesting association with time of death (p = 0.015) in which rs7221412GG individuals had a mean time of death nearly 7 hours later than rs7221412AA/AG. Interpretation: A common polymorphism near PER1 is associated with the timing of human behavioral rhythms, and shows evidence of association with time of death. This may be mediated by differential PER1 expression. These results may facilitate individualized scheduling of shift work, medical treatments, or monitoring of vulnerable patient populations. ANN NEUROL 2012;72:324-334.

Original languageEnglish
Pages (from-to)324-334
Number of pages11
JournalAnnals of Neurology
Volume72
Issue number3
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Fingerprint

Actigraphy
Homozygote
Genetic Association Studies
Physiologic Monitoring
Vulnerable Populations
Pedigree
Circadian Rhythm
Cerebral Cortex
Genes
Monocytes
Sleep
Joints
Mutation
Population
Therapeutics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Lim, A. S. P., Chang, A. M., Shulman, J. M., Raj, T., Chibnik, L. B., Cain, S. W., ... De Jager, P. L. (2012). A common polymorphism near PER1 and the timing of human behavioral rhythms. Annals of Neurology, 72(3), 324-334. https://doi.org/10.1002/ana.23636

A common polymorphism near PER1 and the timing of human behavioral rhythms. / Lim, Andrew S P; Chang, Anne Marie; Shulman, Joshua M.; Raj, Towfique; Chibnik, Lori B.; Cain, Sean W.; Rothamel, Katherine; Benoist, Christophe; Myers, Amanda J; Czeisler, Charles A.; Buchman, Aron S.; Bennett, David A.; Duffy, Jeanne F.; Saper, Clifford B.; De Jager, Philip L.

In: Annals of Neurology, Vol. 72, No. 3, 01.09.2012, p. 324-334.

Research output: Contribution to journalArticle

Lim, ASP, Chang, AM, Shulman, JM, Raj, T, Chibnik, LB, Cain, SW, Rothamel, K, Benoist, C, Myers, AJ, Czeisler, CA, Buchman, AS, Bennett, DA, Duffy, JF, Saper, CB & De Jager, PL 2012, 'A common polymorphism near PER1 and the timing of human behavioral rhythms', Annals of Neurology, vol. 72, no. 3, pp. 324-334. https://doi.org/10.1002/ana.23636
Lim ASP, Chang AM, Shulman JM, Raj T, Chibnik LB, Cain SW et al. A common polymorphism near PER1 and the timing of human behavioral rhythms. Annals of Neurology. 2012 Sep 1;72(3):324-334. https://doi.org/10.1002/ana.23636
Lim, Andrew S P ; Chang, Anne Marie ; Shulman, Joshua M. ; Raj, Towfique ; Chibnik, Lori B. ; Cain, Sean W. ; Rothamel, Katherine ; Benoist, Christophe ; Myers, Amanda J ; Czeisler, Charles A. ; Buchman, Aron S. ; Bennett, David A. ; Duffy, Jeanne F. ; Saper, Clifford B. ; De Jager, Philip L. / A common polymorphism near PER1 and the timing of human behavioral rhythms. In: Annals of Neurology. 2012 ; Vol. 72, No. 3. pp. 324-334.
@article{abd28b78c06e483ea0ef25ffe3a5351b,
title = "A common polymorphism near PER1 and the timing of human behavioral rhythms",
abstract = "Objective: Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self-reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level. Methods: We performed a candidate gene association study with replication, evaluating associations between polymorphisms in homologs of evolutionarily conserved clock genes and the timing of behavioral rhythms measured by actigraphy. For validated polymorphisms, we evaluated associations with transcript expression and time of death in additional cohorts. Results: rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms in both the discovery and replication cohorts (joint p = 2.1 × 10-7). Mean activity timing was delayed by 67 minutes in rs7221412GG versus rs7221412AA homozygotes. rs7221412 also showed a suggestive time-dependent relationship with both cerebral cortex (p = 0.05) and CD14+CD16- monocyte (p = 0.02) PER1 expression and an interesting association with time of death (p = 0.015) in which rs7221412GG individuals had a mean time of death nearly 7 hours later than rs7221412AA/AG. Interpretation: A common polymorphism near PER1 is associated with the timing of human behavioral rhythms, and shows evidence of association with time of death. This may be mediated by differential PER1 expression. These results may facilitate individualized scheduling of shift work, medical treatments, or monitoring of vulnerable patient populations. ANN NEUROL 2012;72:324-334.",
author = "Lim, {Andrew S P} and Chang, {Anne Marie} and Shulman, {Joshua M.} and Towfique Raj and Chibnik, {Lori B.} and Cain, {Sean W.} and Katherine Rothamel and Christophe Benoist and Myers, {Amanda J} and Czeisler, {Charles A.} and Buchman, {Aron S.} and Bennett, {David A.} and Duffy, {Jeanne F.} and Saper, {Clifford B.} and {De Jager}, {Philip L.}",
year = "2012",
month = "9",
day = "1",
doi = "10.1002/ana.23636",
language = "English",
volume = "72",
pages = "324--334",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - A common polymorphism near PER1 and the timing of human behavioral rhythms

AU - Lim, Andrew S P

AU - Chang, Anne Marie

AU - Shulman, Joshua M.

AU - Raj, Towfique

AU - Chibnik, Lori B.

AU - Cain, Sean W.

AU - Rothamel, Katherine

AU - Benoist, Christophe

AU - Myers, Amanda J

AU - Czeisler, Charles A.

AU - Buchman, Aron S.

AU - Bennett, David A.

AU - Duffy, Jeanne F.

AU - Saper, Clifford B.

AU - De Jager, Philip L.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Objective: Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self-reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level. Methods: We performed a candidate gene association study with replication, evaluating associations between polymorphisms in homologs of evolutionarily conserved clock genes and the timing of behavioral rhythms measured by actigraphy. For validated polymorphisms, we evaluated associations with transcript expression and time of death in additional cohorts. Results: rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms in both the discovery and replication cohorts (joint p = 2.1 × 10-7). Mean activity timing was delayed by 67 minutes in rs7221412GG versus rs7221412AA homozygotes. rs7221412 also showed a suggestive time-dependent relationship with both cerebral cortex (p = 0.05) and CD14+CD16- monocyte (p = 0.02) PER1 expression and an interesting association with time of death (p = 0.015) in which rs7221412GG individuals had a mean time of death nearly 7 hours later than rs7221412AA/AG. Interpretation: A common polymorphism near PER1 is associated with the timing of human behavioral rhythms, and shows evidence of association with time of death. This may be mediated by differential PER1 expression. These results may facilitate individualized scheduling of shift work, medical treatments, or monitoring of vulnerable patient populations. ANN NEUROL 2012;72:324-334.

AB - Objective: Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self-reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level. Methods: We performed a candidate gene association study with replication, evaluating associations between polymorphisms in homologs of evolutionarily conserved clock genes and the timing of behavioral rhythms measured by actigraphy. For validated polymorphisms, we evaluated associations with transcript expression and time of death in additional cohorts. Results: rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms in both the discovery and replication cohorts (joint p = 2.1 × 10-7). Mean activity timing was delayed by 67 minutes in rs7221412GG versus rs7221412AA homozygotes. rs7221412 also showed a suggestive time-dependent relationship with both cerebral cortex (p = 0.05) and CD14+CD16- monocyte (p = 0.02) PER1 expression and an interesting association with time of death (p = 0.015) in which rs7221412GG individuals had a mean time of death nearly 7 hours later than rs7221412AA/AG. Interpretation: A common polymorphism near PER1 is associated with the timing of human behavioral rhythms, and shows evidence of association with time of death. This may be mediated by differential PER1 expression. These results may facilitate individualized scheduling of shift work, medical treatments, or monitoring of vulnerable patient populations. ANN NEUROL 2012;72:324-334.

UR - http://www.scopus.com/inward/record.url?scp=84867059623&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867059623&partnerID=8YFLogxK

U2 - 10.1002/ana.23636

DO - 10.1002/ana.23636

M3 - Article

C2 - 23034908

AN - SCOPUS:84867059623

VL - 72

SP - 324

EP - 334

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -