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In caffeine (2 \u00d7 2.5 mg\/kg\/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-\u03b1 SNP A allele appear to be more sensitive than homozygote G\/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G\/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-\u03b1, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).<\/jats:p>","DOI":"10.3390\/genes12040555","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882)"],"prefix":"10.3390","volume":"12","author":[{"given":"M\u00e9gane","family":"Erblang","sequence":"first","affiliation":[{"name":"Institut de Recherche Biom\u00e9dicale des Arm\u00e9es (IRBA), 91190 Br\u00e9tigny sur Orge, France"},{"name":"EA VIFASOM (EA 7330 Vigilance, Fatigue, Sommeil et Sant\u00e9 Publique), Universit\u00e9 de Paris, 75004 Paris, France"},{"name":"LBEPS, Univ Evry, IRBA, Universit\u00e9 Paris Saclay, 91025 Evry, 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