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

• 발행기관: 대한신경정신의학회
• 저자명: Daniel F. Kripke Walter T. Klimecki Caroline M. Nievergelt Katharine M. Rex Sarah S. Murray Tatyana
• 간행물 정보: 『Psychiatry Investigation』제11권 제4호, 345~362쪽, 전체 18쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2014.10.31

영문 초록

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.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

SUPPLEMENTARY MATERIALS

ACKNOWLEDGEMENTS

REFERENCES

키워드

Delayed sleep phase syndrome Non-24 hour sleep-wake disorder Bipolar disorder BHLHE40 NFIL3 RORC