ESRS 2016 Podium Sessions Opening Session O90 Melatonin signaling pathway gene linked to intolerance to shift work S. Sulkava 1,2 , H. M. Ollila 3 , J. Alasaari 1 , S. Puttonen 4 , M. H€ arm€ a 4 , K. Viitasalo 5 , J. Lindstr€ om 1 , A. Toivola 1 , R. Sulkava 6 , M. Kivim€ aki 4 , J. Vahtera 7 , T. Partonen 1 , K. Silander 1 , T. Porkka-Heiskanen 2 and T. Paunio 1 1 National Institute for Health and Welfare, 2 University of Helsinki, Helsinki, Finla, 3 Stanford University, Stanford, CA, USA, 4 Finnish Institute of Occupational Health, Helsinki, 5 Finnair Health Services, Vantaa, 6 University of Eastern Finland, Kuopio, 7 University of Turku, Turku, Finland Objectives: Tolerance to shift work varies; only some shift workers suffer work-related symptoms, such as disturbed sleep, fatigue, and job-related exhaustion. Our aim was to explore molecular genetic background for intolerance to shift work. Methods: We assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaus- tion subscale of the Maslach Burnout Inventory - General Survey. The genome-wide association study (GWAS) was carried out using Illumina’s Human 610-Quad BeadChip (n = 176). The most signifi- cant findings from GWAS were further analyzed in three shift workers samples (n = 753 in the meta-analysis). To examine potential epigenetic mechanisms to mediate genetic associations, methylation analyses with Illumina Human Methylation 450K platform were performed using blood cell samples from the shift workers. Results: Replications of the GWAS signal in two of the samples (P < 0.05) and genome-wide significance in the meta-analysis (P < 5 9 10 -8 ) indicated an association of job-related exhaustion in shift workers with a variant, located downstream of a melatonin pathway gene (M1). The risk allele was associated with relative DNA hypermethylation in the 5’ regulatory region of M1. Conclusions: We have identified a risk variant for job-related exhaustion in shift workers located near a melatonin signaling pathway gene. The effect of the risk variant may be mediated by epigenetic mechanisms, which potentially lead to reduced melatonin signaling in the brain. These results demonstrate a link between melatonin signaling, a key circadian regulatory mechanism, and tolerance to shift work. Disclosure: Nothing to disclose. O91 Circadian and homeostatic sleep pressure modulate fMRI correlates of vigilant attention V. Muto 1,2 , M. Jaspar 1,2 , C. Meyer 1 , C. Kuss e 1 , S. L. Chellappa 1 , C. Degueldre 1 , E. Balteau 1 , A. Shaffii-Le Bourdiec 1 , A. Luxen 1 , B. Middleton 3 , S. N. Archer 3 , C. Phillips 1,4 , F. Collette 1,2 , G. Vandewalle 1 , D.-J. Dijk 3 and P. Maquet 1,5 1 GIGA-Cyclotron Research Centre-In vivo Imaging, University of Li  ege, 2 Psychology and Cognitive Neuroscience Research Unit, University of Li  ege, Li  ege, Belgium, 3 Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom, 4 Department of Electrical Engineering and Computer Science, University of Li  ege, 5 Department of Neurology, CHU Li  ege, Li  ege, Belgium Objective: Vigilant attention is believed to participate in cognitive performance decline during sleep deprivation. We assessed fMRI responses to the psychomotor vigilance task, during sleep loss, to investigate possible circadian and homeostatic sleep need modula- tions. Methods: Thirty-three healthy young volunteers (age 21.12  1.7; 17 women) participated in a 42 h sleep deprivation protocol under constant routine conditions. Cerebral responses were quantified across 12 fMRI sessions during sleep deprivation and one fMRI session following recovery sleep. We identified circadian modulation of brain response during intermediate RT by fitting a 24-h sine and a cosine function to the data which were aligned to the onset of melatonin. From the parameter estimates of the sine and cosine functions, we derived the amplitude and circadian phase of the brain responses. The effect of homeostatic sleep pressure was modelled as monotonic increase with time awake. Results: A significant circadian modulation was observed over almost the entire cortex (p FDR whole brain < 0.05). Interestingly, the phase of the circadian modulation varied across brain regions (Friedman, v 2 = 30.13; df = 4; P = 4.60 9 10 -6 ). A significant effect of homeostatic sleep pressure (all P corr < 0.05) was observed in a large set of cortical areas, characterized by a decrease in brain response with time spent awake. Conclusion: Our results indicate that brain correlates of vigilant attention are modulated by both circadian and homeostatic sleep factors. Moreover, the data show, for the first time, evidence for a local circadian modulation of brain activity. Research funded by: FNRS, FMRE, WELBIO, BBSRC, Baron Clerdent, ARC, ULg, FEDER, RADIOMED. Disclosure: Nothing to disclose. ª 2016 The Authors Journal of Sleep Research ª 2016 European Sleep Research Society, JSR 25 (Suppl. 1),5–376 5