NDLI: Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

Content Provider	PubMed Central
Author	Kripke, Daniel F. Klimecki, Walter T. Nievergelt, Caroline M. Rex, Katharine M. Murray, Sarah S. Shekhtman, Tatyana Tranah, Gregory J. Loving, Richard T. Lee, Heon-jeong Rhee, Min Kyu Shadan, Farhad F. Poceta, J. Steven Jamil, Shazia M. Kline, Lawrence E. Kelsoe, John R.
Copyright Year	2014
Abstract	People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.
Related Links	http://dx.doi.org/10.4306/pi.2014.11.4.345
Ending Page	362
Page Count	18
Starting Page	345
File Format	PDF
ISSN	17383684
e-ISSN	19763026
Journal	Psychiatry Investigation
Issue Number	4
Volume Number	11
Language	English
Publisher	Korean Neuropsychiatric Association
Publisher Date	2014-01-01
Access Restriction	Open
Rights Holder	Korean Neuropsychiatric Association
Subject Keyword	Biological Psychiatry Psychiatry and Mental health Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biological Psychiatry Psychiatry and Mental Health

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