期刊
ANNALS OF NEUROLOGY
卷 72, 期 3, 页码 324-334出版社
WILEY
DOI: 10.1002/ana.23636
关键词
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资金
- Canadian Institutes of Health Research Bisby Fellowship
- American Academy of Neurology Clinical Research Training Fellowship
- Dana Foundation Clinical Neuroscience Grant
- NIH NINDS [R01NS072337]
- NIH NIA [R01AG024480, R01AG017917, R01AG015819, R01AG030146, P30AG010161, P01 AG009975, R01AG034504]
- NIH NCCAM [AT002571]
- NIH NHLBI [H080978]
- NIH NIGMS [RC2GM092080]
- AFOSR [FA 9550-060080/O5LN132]
- Translational Genomics Research Institute
- NIA
- National Alzheimer's Coordinating Center (NIA) [U01 AG016976]
- John Hopkins Alzheimer's Disease Research Center (NIA) [AG05146]
- University of California, Los Angeles (NIA) [P50 AG16570]
- Kathleen Price Bryan Brain Bank
- Duke University Medical Center (NIA) [AG05128]
- National Institute of Neurological Disorders and Stroke [NS39764]
- National Institute of Mental Health [MH60451]
- GlaxoSmithKline
- University of Michigan (NIA) [P50-AG08671]
- University of Kentucky (NIA) [AG05144]
- Washington University, St Louis Alzheimer's Disease Research Center (NIA) [P50AG05681]
- University of Washington, Seattle (NIA) [P50 AG05136]
- Boston University Alzheimer's Disease Research Center (NIA) [P30-AG13846]
- Sun Health Research Institute, Sun City, Arizona (NIA) [P30-AG19610]
- Rush Alzheimer's Disease Center (NIA) [AG10161]
- NIH
- Parkinson's Study Group/Parkinson's Disease Foundation
- Burroughs Wellcome Fund Career Award for Career Awards for Medical Scientists
- Clinical Investigator Training Program
- Cephalon
- Koninklijke Philips Electronics
- ResMed
- Jazz Pharmaceuticals
- Philips Respironics
- Takeda Pharmaceuticals
- Sanofi-Aventis
- Sepracor
- Tempur-Pedic
- Jordan's Furniture
- Sleep Health Centers
- Committee for Interns and Residents
- Boehringer Ingelheim Pharmaceuticals
- Gerald McGinnis
- Hypnion
- Merck
- Pfizer
- Sealy
- Simmons
- Spring Aire
- Accreditation Council of Graduate Medical Education
- Alliance for Epilepsy Research
- Duke University School of Medicine
- Harvard School of Public Health
- Mount Sinai School of Medicine
- National Academy of Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH)
- North East Sleep Society
- Office of Rare Diseases Research (NIH)
- Society for Obstetric Anesthesia and Perinatology (SOAP)
- St. Luke's Roosevelt Hospital
- University of Pittsburgh
- University of Virginia Medical School
- University of Washington Medical Center
- University of Wisconsin Medical School
- American Academy of Sleep Medicine
- National Sleep Foundation
- New England College of Occupational and Environmental Medicine (NECOEM)
- Rockpointe/Cephalon
- University of Chicago
- University of Colorado
- Hokkaido University Graduate School of Medicine
- Japan Aerospace Exploration Agency (JAXA)
- LOTTE Health Products
- Sleep Research Society
- Stress Research Institute (University of Stockholm)
- World Federation of Sleep Research and Sleep Medicine Societies
- McGraw Hill
- New York Times
- Penguin Press
- Massachusetts Medical Society/NEJM
- Philips-Respironics
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 x 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;72:324334.
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