Genetic liability for insomnia and hypersomnia differ among individuals with bipolar disorder (BD) I and II, according to case-control study results published in JAMA Psychiatry.

Katie Lewis, PhD, of the Medical Research Council Centre for Neuropsychiatric Genetics and Genomics at the Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University in the United Kingdom, and colleagues examined potential relationships between BD subtype differences and sleep disturbances that could be attributed to distinct genetic profiles.

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The researchers recruited patients from the Bipolar Disorder Research Network and determined subtype via semi-structured interviews and case notes. They looked at polygenic risk score (PRS) based on alleles from genome-wide association studies of insomnia, daytime sleepiness, sleep duration, and chronotype. Sleep traits of study patients were assessed by questionnaire.

Multinomial logistic regressions were performed to determine relationships between PRS, sleep traits, and BD subtypes. Secondary analyses involved 2-sample Mendelian randomization to examine causal associations. Finally, replication of study findings were attempted in a Swedish cohort.

In the total British sample of patients with BD (N=4672; 67.0% women), 3404 had BD I and 1268 had BD II. Compared with controls (N=5714), the PRS for insomnia was significantly associated with a diagnosis of BD II (relative risk [RR], 1.14; P =8.26×10-5). Furthermore, direct tests also demonstrated insomnia PRS was significantly associated with BD II compared with BD I (RR, 1.16; P =1.95×10-4).

Sleep-duration PRS was associated with BD I compared to controls (RR, 1.10; P =1.13×10-5), and the RR for sleep-duration PRS in patients with BD I compared with BD II was 1.11 (P = 1.69×10-3). However, in Mendelian randomization analyses, the researchers did not find any causal relationships between subtypes and these respective sleep traits.

The Swedish replication sample included 4366 patients (61.8% women; 2627 BD I; 1739 BD II), as well as 6091 controls. Results demonstrated similar associations between BD II and insomnia PRS (RR, 1.07; P =.013), as well as those between BD I and sleep duration PRS (RR, 1.11; P =1.72×10-5) compared with controls. However, there was also a significant correlation between sleep duration PRS and increased risk for BD II (RR, 1.06; P =.042).

The key findings of the study, conducted in the world’s largest BD cohort with genotypic and phenotypic data, offer potential sleep-related genetic underpinnings for BD diagnostic groups. However, the results may be limited by the inability to adjust for age and education. Both study cohorts were also entirely of European descent.

“Clinical and biological heterogeneity, combined with a classification that is not grounded in biology, are obstacles to advancing BD research,” the researchers wrote. They called for further studies in younger samples, as well as investigations of potential mechanisms underlying subtype genetic liability differences.

Reference

Lewis KJS, Richards A, Karlsson R, et al. Comparison of genetic liability for sleep traits among individuals with bipolar disorder I or II and control participants. JAMA Psychiatry. 2019. doi:10.1001/jamapsychiatry.2019.4079