Summary: Irish researchers report genetic links between sleep characteristics and several neuropsychiatric and neurodevelopmental conditions. Using large-scale polygenic risk score analysis, they found that genetic liability for autism and schizophrenia is associated with an evening chronotype (a tendency toward “night owl” behaviour), while genetic liability for ADHD, schizophrenia, and bipolar disorder is associated with insomnia. These genetic connections shed light on biological pathways that may underlie sleep disruption in affected individuals and could guide future treatment research.
Key Facts:
- Genetic predisposition for autism and schizophrenia is linked to an evening chronotype.
- Genetic predisposition for ADHD, schizophrenia, and bipolar disorder is linked to insomnia.
- Identifying shared genetic signals may inform new approaches to treating sleep disturbances in neuropsychiatric conditions.
Source: European Society of Human Genetics
Disturbed sleep is highly prevalent across many neuropsychiatric and neurodevelopmental conditions (NDPCs), including autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder.
While it is intuitive that the symptoms of these disorders can disrupt sleep, and conversely that poor sleep can exacerbate psychiatric symptoms, the new study focuses on the genetic relationships between these disorders and circadian behaviour — commonly described as chronotype (for example, “night owl” versus “early bird”).
Presented at the European Society of Human Genetics annual meeting, the work was led by Dr Laura Fahey from the Family Genomics Research Group at Maynooth University, Ireland. The team applied polygenic risk score (PRS) methods to examine whether the inherited genetic risk for several NDPCs predicts self-reported chronotype and insomnia symptoms in a very large cohort.
Specifically, the researchers calculated polygenic scores derived from genome-wide association studies of neuropsychiatric and neurodevelopmental disorders and tested how well these scores predicted sleep traits in over 409,000 participants from the UK Biobank. By linking genetic liability for psychiatric conditions with sleep-related phenotypes, the analysis explores shared genetic architecture and potential biological mechanisms.
The results reinforced previously observed genetic correlations and extended them. Polygenic scores for autism and schizophrenia were associated with a tendency toward an evening chronotype, while polygenic scores for ADHD, schizophrenia, and bipolar disorder were associated with greater likelihood of reporting insomnia symptoms. The team also reported novel associations — for example, links between bipolar disorder and chronotype, and between insomnia and autism — which had not been widely described before.
These findings provide genetic evidence that some sleep and circadian traits share common biological roots with neuropsychiatric disorders. Dr Fahey notes that such overlap could open research avenues for developing targeted interventions to improve sleep and circadian regulation in affected patients, potentially reducing symptom burden and improving quality of life.
One pathway of interest identified in the analysis was the NRF2-KEAP1 pathway, which showed enrichment for shared genetic variation between bipolar disorder and chronotype. The NRF2 pathway has been implicated previously in studies of bipolar disorder and schizophrenia, and NRF2 activity is known to be regulated in a circadian manner by core clock genes. This convergence suggests a plausible biological route linking circadian regulation and mood disorder biology.
However, the researchers also emphasize caution. For several of the other sleep–NDPC phenotype pairs, they did not find significant pathway enrichment. For example, although ADHD and insomnia showed a strong genome-wide genetic correlation, no single biological pathway emerged as disproportionately enriched for the shared genetic signal. This may reflect a highly polygenic architecture in which many genes across diverse pathways contribute small effects, or it could indicate that shared variation concentrates in cell- or tissue-specific mechanisms not captured by the pathway analyses performed.
The study has limitations the authors acknowledge. The UK Biobank sample used in this analysis is predominantly of white British ancestry, so the team plans to expand their work to more diverse populations to determine whether these genetic relationships generalize across ancestries. Broader analyses will be important for developing predictive biomarkers and preventive strategies that are equitable and effective across different groups.
Looking forward, the researchers propose several next steps: investigating how genetic variation in implicated pathways affects gene expression and cellular function, identifying patient subgroups with specific molecular signatures, and applying complementary genetic methods to map the full genetic architecture of sleep and circadian disturbances in NDPCs, including both common and rare variants.
Dr Fahey summarizes the opportunity: by clarifying which genetic factors are shared between sleep traits and neuropsychiatric disorders, scientists can better prioritize biological targets for study and ultimately aim to translate genetic knowledge into interventions that improve sleep and mental health outcomes.
Professor Alexandre Reymond of the Center for Integrative Genomics, University of Lausanne, highlighted the concept of pleiotropy — where the same molecular pathways influence multiple distinct traits — noting that if direct pleiotropy is present (one trait causally influencing another), these genetic signals may offer hints toward therapeutic approaches.
Note:
* Gene-regulation pathways modulate when and how genes are turned on or off. These regulatory processes determine protein production in cells and are essential for nearly all biological functions, including those that govern sleep and circadian rhythms.
About this genetics, sleep and ASD research news
Author: Mary Rice
Source: European Society of Human Genetics
Contact: Mary Rice – European Society of Human Genetics
Image: The image is credited to Neuroscience News
Original Research: The findings were presented at the European Society of Human Genetics annual conference