ORCID Profile
0000-0001-6101-2855
Current Organisations
Massachusetts General Hospital
,
Broad Institute
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Publisher: Cold Spring Harbor Laboratory
Date: 19-04-2018
DOI: 10.1101/303941
Abstract: Using genome-wide data from 697,828 research participants from 23andMe and UK Biobank, we increase the number of identified loci associated with being a morning person, a behavioural indicator of a person’s underlying circadian rhythm, from 24 to 351. Using data from 85,760 in iduals with activity-monitor derived measures of sleep timing we show that the chronotype loci influence sleep timing: the mean sleep timing of the 5% of in iduals carrying the most “morningness” alleles was 25 minutes earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. We provide evidence that being a morning person is causally associated with better mental health but does not appear to affect BMI or Type 2 diabetes. This study offers new insights into the biology of circadian rhythms and links to disease in humans.
Publisher: Cold Spring Harbor Laboratory
Date: 03-06-2019
DOI: 10.1101/652966
Abstract: Sleep-disordered breathing (SDB) is a common disorder associated with significant morbidity. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program we report the first whole-genome sequence analysis of SDB. We identified 4 rare gene-based associations with SDB traits in 7,988 in iduals of erse ancestry and 4 replicated common variant associations with inclusion of additional s les (n=13,257). We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10 −8 ) on chromosome X with ARMCX3 . Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Results highlighted associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis and HIF1A -mediated hypoxic response.
Publisher: Oxford University Press (OUP)
Date: 21-09-2023
Publisher: Elsevier BV
Date: 12-2021
Publisher: Cold Spring Harbor Laboratory
Date: 17-10-2022
DOI: 10.1101/2022.10.16.22280934
Abstract: Circadian rhythm disturbance is a common feature of many psychiatric disorders. Light is the primary input to the circadian clock, with daytime light strengthening rhythms and night light disrupting them. Therefore, habitual light exposure may represent an environmental risk factor for susceptibility to psychiatric disorders. We performed the largest to-date cross-sectional analysis of light, sleep, physical activity, and mental health ( n = 86,772 adults aged 62.4 ± 7.4 years 57% women). We examined the independent association of day and night light exposure with covariate-adjusted risk for psychiatric disorders and self-harm. Greater night light exposure was associated with increased risk for major depressive disorder, generalized anxiety disorder, PTSD, psychosis, bipolar disorder, and self-harm behavior. Independent of night light, greater day light exposure was associated with reduced risk for major depressive disorder, PTSD, psychosis, and self-harm behavior. These findings were robust to adjustment for sociodemographics, photoperiod, physical activity, and sleep quality. Avoiding light at night and seeking light during the day may be a simple and effective, non-pharmacological means of broadly improving mental health.
Publisher: Cold Spring Harbor Laboratory
Date: 08-09-2023
Publisher: Cold Spring Harbor Laboratory
Date: 30-06-2022
DOI: 10.1101/2022.06.29.22277078
Abstract: Light is the primary stimulus for synchronizing the circadian clock in humans. There are very large interin idual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interin idual differences. We performed a genome-wide gene-by-environment interaction study (GWIS) in 280,897 in iduals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (in idual time of day preference), acting as ‘light sensitivity’ variants for the impact of daylight on the circadian system. We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634 p 5×10 −8 ), where additional minor alleles were found to enhance the morningness effect of daytime light exposure ( β GxE = -.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and in Per2 + hypothalamic neurons. Linkage disequilibrium score regression identified significant genetic correlations of the light sensitivity GWIS with chronotype and sleep duration, such that greater light sensitivity was associated with later chronotype, greater insomnia symptoms and shorter sleep duration. Greater light sensitivity was also genetically correlated with greater risk for PTSD. This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental health.
No related grants have been discovered for Jacqueline Lane.