Human CRY1 variants associate with attention deficit/hyperactivity disorder.

Area of Science:

• Genetics
• Neuroscience
• Chronobiology

Background:

• Attention deficit/hyperactivity disorder (ADHD) is a common, heritable condition often co-occurring with insomnia, anxiety, and depression.
• Circadian rhythm disruptions are increasingly recognized as contributing factors in psychiatric disorders.

Purpose of the Study:

• To investigate the role of circadian clock gene variations in individuals with combined ADHD and insomnia.
• To identify potential genetic markers for ADHD and related sleep and mood disturbances.

Main Methods:

• Reverse phenotyping approach in multigenerational families.
• Exome sequencing in an independent cohort of ADHD and insomnia patients.
• Phenome-wide association study in a large European cohort.

Main Results:

• Heterozygous coding variations in the cryptochrome 1 (CRY1) gene were identified in families with combined ADHD and insomnia.
• A specific variant, CRY1Δ11, found in ~1% of Europeans, was significantly associated with ADHD, insomnia, major depressive disorder, and anxiety.
• Another variant, CRY1Δ6, was linked to ADHD and delayed sleep phase disorder (DSPD).

Conclusions:

• Circadian clock gene variations, particularly in CRY1, contribute to a distinct group of psychiatric disorders characterized by circadian rhythm dysfunction.
• CRY1 variants may serve as diagnostic and therapeutic markers for these "circiatric" disorders.