Relationship between Polygenic Risk Score and the Hypnotics in Bipolar I Disorder
Hyeon Woo Lee1, Bun-Hee Lee2, Tatyana Shekhtman3, Young-Min Park1, John R. Kelsoe3
1Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
2Maum and Maum Psychiatric Clinic, Seoul, Korea
3Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Correspondence to: John R. Kelsoe
Department of Psychiatry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA

Young-Min Park
Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang 10380, Korea
Received: December 11, 2023; Revised: February 2, 2024; Accepted: February 4, 2024; Published online: March 7, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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Objective: Bipolar disorder (BD) is marked by significant change in mood and energy levels with sleep disturbance a common feature, resulting in diminished quality of life and impaired daily functioning. This study assessed the association between BD-polygenic risk scores (PRS) and hypnotics in bipolar I disorder (BD-I) patients.
Methods: Large-sample data were collected from the genome-wide association study of a multicenter Bipolar Genomic Study, and 1,394 BD-I patients with available medication information were divided into two groups depending on whether they used hypnotics or not. The Diagnostic Interview for Genetic Studies (DIGS) score was used to assess the clinical manifestations and function of the participants and the association between the use of hypnotics and genetic risk was analyzed.
Results: Of the 1,394 total participants, 556 (40%) patients received hypnotics, mostly benzodiazepines, administered singly or in combination with other sleeping agents such as, Z-drugs, melatonin-related drugs, and trazodone. The DIGS score was significantly higher for negative categories in the group prescribed hypnotics as was the BD-PRS score, according to the four p value thresholds (p = 0.3, 0.2, 0.1, and 0.05). Logistic regression analysis confirmed a statistically significant association between the BD-PRS and hypnotic use.
Conclusion: Our results suggest an association between hypnotic use and genetic susceptibility to BD. Sleep disturbances in participants were based on the prescription status of hypnotics supporting the hypothesis that sleep disturbances may be associated with genetic aspects of BD-I. Further genetic studies on genetic overlaps between BD and specific phenotypes or medication responses are required.
Keywords: Bipolar disorder; Polygenic risk score; Hypnotics; Sleep disturbance

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