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Dai, X., Williams, G.J. 
ORCID: 0000-0001-7689-1231, Groeger, J.A. ORCID: 0000-0002-3582-1058, Jones, G. ORCID: 0000-0003-3867-9947, Brookes, K. ORCID: 0000-0003-2427-2513, Zhou, W., Du, W. ORCID: 0000-0002-5115-7214 and Hua, J.,
2024.
The role of circadian rhythms and sleep in the aetiology of autism spectrum disorder and attention-deficit/hyperactivity disorder: new evidence from bidirectional two-sample Mendelian randomization analysis.
Autism.
ISSN 1362-3613
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Abstract
Increasing evidence highlights the role of disrupted circadian rhythms in the neural dysfunctions and sleep disturbances observed in autism spectrum disorder and attention-deficit/hyperactivity disorder. However, the causality and directionality of these associations remain unclear. In this study, we employed a bidirectional two-sample Mendelian randomization framework, leveraging genome-wide association study data from the UK Biobank (n = 85,670) and FinnGen (n = 377,277). Genetic variants served as instrumental variables to infer causation, and objective accelerometer-derived metrics identified circadian rhythm and sleep genetic instruments. The results showed that the timing of the most active 10 h was significantly linked to higher odds of autism spectrum disorder and attention-deficit/hyperactivity disorder. Independently, higher sleep efficiency predicted a lower risk of autism spectrum disorder, while attention-deficit/hyperactivity disorder was linked to an increase in nocturnal sleep episodes. Heterogeneity and sensitivity analyses confirmed these findings. Our study establishes causal links between circadian alterations and autism spectrum disorder and attention-deficit/hyperactivity disorder, distinguishing the independent and protective role of sleep efficiency in autism spectrum disorder from circadian rhythms. In attention-deficit/hyperactivity disorder, however, disrupted sleep appears as a consequence, not a cause. These insights highlight divergent interactions with sleep factors in autism spectrum disorder and attention-deficit/hyperactivity disorder, laying the groundwork for tailored therapeutic strategies that recognize the distinct influences of sleep quality and circadian rhythms in each disorder.
| Item Type: | Journal article | ||||||
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| Publication Title: | Autism | ||||||
| Creators: | Dai, X., Williams, G.J., Groeger, J.A., Jones, G., Brookes, K., Zhou, W., Du, W. and Hua, J. | ||||||
| Publisher: | SAGE Publications | ||||||
| Date: | 13 June 2024 | ||||||
| ISSN: | 1362-3613 | ||||||
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| Rights: | © the author(s) 2024. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). | ||||||
| Divisions: | Schools > School of Science and Technology Schools > School of Social Sciences |
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| Record created by: | Jonathan Gallacher | ||||||
| Date Added: | 13 Jun 2024 16:47 | ||||||
| Last Modified: | 13 Jun 2024 16:47 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/51565 |
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