Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans

Area of Science:

• Neuroscience
• Genetics
• Sleep Science

Background:

• Slow-wave oscillations during non-rapid eye movement (NREM) sleep are crucial for restorative functions.
• The adenosine deaminase (ADA) gene, specifically the c.22G>A polymorphism (rs73598374), influences adenosine metabolism and baseline sleep patterns.

Purpose of the Study:

• To investigate the impact of the ADA c.22G>A polymorphism on cognitive functions.
• To determine if this polymorphism modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation.

Main Methods:

• Cognitive functions (attention, learning, memory, executive functioning) were assessed in healthy adults with different ADA genotypes (G/A vs. G/G).
• Sleep and sleep EEG were analyzed before and after sleep deprivation in prospectively matched G/A and G/G genotype groups.
• Salivary α-amylase levels were measured as a biochemical marker.

Main Results:

• Individuals with the G/A genotype (variant allele carriers) showed poorer performance on attention tasks compared to G/G homozygotes.
• G/A genotype subjects exhibited higher deep sleep and specific NREM EEG oscillations (0.75-1.5 Hz).
• Sleep deprivation led to reduced attention and vigor, and increased EEG alpha activity, sleepiness, fatigue, and salivary α-amylase in G/A individuals compared to G/G.

Conclusions:

• The ADA c.22G>A polymorphism elevates homeostatic sleep pressure.
• This genetic variation significantly influences sleep quality and waking cognitive performance in humans.
• Reduced ADA activity plays a critical role in modulating sleep-wake regulation and associated physiological responses.