15 research outputs found
Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
This is the final version. Available on open access from Nature Research via the DOI in this recordData Availability:
The data that support the findings of this study from the UK BioBank will be made available at https://sleepgenetics.org and the underlying genotype and phenotype data are available through application to the UK Biobank. Other phenotype data are available on request, due to privacy or other restrictions, through co-corresponding author Dr. Scheer ([email protected]).The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.European CommissionWellcome TrustMedical Research Council (MRC
Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology
The risk of type 2 diabetes (T2D) is increased by abnormalities
in sleep quantity and quality, circadian alignment,
and melatonin regulation. A common genetic variant in a
receptor for the circadian-regulated hormone melatonin
(MTNR1B) is associated with increased fasting blood glucose
and risk of T2D, but whether sleep or circadian disruption
mediates this risk is unknown. We aimed to test if
MTNR1B diabetes risk variant rs10830963 associates with
measures of sleep or circadian physiology in intensive inlaboratory
protocols (n = 58–96) or cross-sectional studies
with sleep quantity and quality and timing measures from
self-report (n = 4,307–10,332), actigraphy (n = 1,513), or
polysomnography (n = 3,021). In the in-laboratory studies,
we found a significant association with a substantially longer
duration of elevated melatonin levels (41 min) and delayed
circadian phase of dim-light melatonin offset (1.37 h),
partially mediated through delayed offset of melatonin
synthesis. Furthermore, increased T2D risk in MTNR1B
risk allele carriers was more pronounced in early risers
versus late risers as determined by 7 days of actigraphy.
Our results provide the surprising insight that the MTNR1B
risk allele influences dynamics of melatonin secretion,
generating a novel hypothesis that the MTNR1B risk allele
may extend the duration of endogenous melatonin production
later into the morning and that early waking may
magnify the diabetes risk conferred by the risk allele
Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans
Abstract The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system