A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain

Tichelman, N. L.; Foerges, A. L.; Elmenhorst, E.-M.; Lange, D.; Hennecke, E.; Baur, D. M.; Beer, S.; Kroll, T.; Neumaier, B.; Bauer, A.; Landolt, H.-P.; Aeschbach, D.; Elmenhorst, D.

doi:10.1101/2023.03.01.530170

bioRxiv · 10.1101/2023.03.01.530170

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain

Tichelman, N. L.·Foerges, A. L.·Elmenhorst, E.-M.·Lange, D.·Hennecke, E.·Baur, D. M.·Beer, S.·Kroll, T.·Neumaier, B.·Bauer, A.·Landolt, H.-P.·Aeschbach, D.·Elmenhorst, D.

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Abstract

The EEG alpha rhythm (8-13 Hz) is one of the most salient human brain activity rhythms. Spectral power in the alpha range in wakefulness and sleep varies among individuals based on genetical predisposition, yet knowledge about the underlying genes is scarce. The EEG alpha oscillations are related to cerebral energy metabolism and modulated by the level of attention and vigilance. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate (ATP) breakdown and acts as a sleep promoting molecule by activitating A1 and A2A adenosine receptors. We quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1 adenosine receptor availability by positron emission tomography with 18F-CPFPX, in a large sample of healthy volunteers carrying different alleles of gene variant rs5751876 of ADORA2A encoding A2A adenosine receptors. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37) = 2.35, p = 0.014, Wilks {Lambda} = 0.467). Across considered brain regions an effect of ADORA2A genotype on A1 adenosine receptor binding potential was found (F(18,40) = 2.62, p = 0.006, Wilks {Lambda} = 0.459) and after correction for multiple testing this effect was shown to be significant for circumscribed occipital region of calcarine fissures. A correlation between individual differences in oscillatory alpha power and adenosine receptor availability was found for the subgroup of female participants only. In conclusion: a genetic variation in the adenosinergic system affects individual alpha power, although a direct modulatory effect via the A1AR has been demonstrated for females only.

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Tichelman, N. L., Foerges, A. L., Elmenhorst, E.-M., Lange, D., Hennecke, E., Baur, D. M., Beer, S., Kroll, T., Neumaier, B., Bauer, A., Landolt, H.-P., Aeschbach, D., Elmenhorst, D.. 2023-03-02. A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain. https://doi.org/10.1101/2023.03.01.530170

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