Circadian and sleep-related polygenic scores in relation to lithium treatment response in bipolar disorder

Apr 16, 2026Neuropsychobiology

Genetic risk for sleep and daily rhythm traits linked to lithium response in bipolar disorder

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Abstract

The polygenic score for ease of getting up was significantly associated with lithium response, explaining 9.989% of the variance.

Higher genetic predisposition for ease of getting up is linked to increased odds of a positive response to lithium treatment.
The odds ratio for a good response to lithium treatment in individuals with a higher genetic predisposition for ease of getting up is 5.143.
Significant associations were found using logistic regression models, with FDR-adjusted p-values indicating statistical relevance.
The study highlights the potential role of sleep traits in influencing treatment outcomes for bipolar disorder.

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Introduction Circadian rhythms are reflected through sleep-wake patterns and chronotype. Patients with bipolar disorder (BD) frequently exhibit disrupted sleep patterns, and a tendency for evening chronotype. Also, genetic risk factors for BD partially overlap with those influencing sleep traits. Lithium (Li), the first-line therapy for BD, stabilizes circadian rhythms and promotes morningness in responders. This study aimed to evaluate whether the polygenic burden of sleep-related traits is associated with Li response in BD patients. Methods A total of 114 European-ancestry BD patients were categorized as Li responders (N=79) or non-responders (N=35), based on the reduction of 50% of the episodes. Polygenic scores (PGS) for chronotype, daytime dozing, ease of getting up, insomnia, morningness, napping, sleep duration, and snoring were calculated using PRS-CS. Associations between each PGS and Li response were tested using logistic regression models. Comparisons were made between the extreme quartiles of each PGS. Results The polygenic score for ease of getting up was significantly associated with Li response, explaining 9.989% of the variance based on Nagelkerke's pseudo-R² (FDR-adjusted p-value= 0.046). Additionally, individuals with a higher genetic predisposition for ease of getting up had increased odds of a good response (FDR-adjusted p-value= 0.039; OR= 5.143; 95% CI= 1.537-17.209). Conclusion The study suggests that a higher genetic predisposition for ease of getting up in the morning may increase the likelihood of responding to Li treatment in BD patients. Our study aligns with previous evidence, highlighting the importance of sleep and chronotype patterns in response to Li in BD patients.

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Circadian and sleep-related polygenic scores in relation to lithium treatment response in bipolar disorder

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