Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances

Rackeb Tesfaye (1) , Guillaume Huguet (2) , Zoe Schmilovich (1) , Thomas Renne (2) , Mor Absa Loum (2) , Elise Douard (2) , Zohra Saci (2) , Martineau Jean-Louis (2) , Jean-Luc MARTINOT (3, 4) , Rob Whelan (5) , Sylvane Desrivieres (6) , Andreas Heinz (7) , Gunter Schumann (8, 6) , Caroline Hayward (9) , Mayada Elsabbagh , Sebastien Jacquemont (2)

1 McGill University = Université McGill [Montréal, Canada]
2 UdeM - Université de Montréal
3 CB - CB - Centre Borelli - UMR 9010
4 ERL Inserm U1299 - Trajectoires développementales en psychiatrie : mesures et modélisations
5 Trinity College Dublin
6 King‘s College London
7 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
8 Fudan University [Shanghai]
9 Edin. - University of Edinburgh

Sleep disturbance is prevalent in youth with Autism Spectrum Disorder (ASD). Researchers have posited that circadian dysfunction may contribute to sleep problems or exacerbate ASD symptomatology. However, there is limited genetic evidence of this. It is also unclear how insomnia risk genes identified through GWAS in general populations are related to ASD and common sleep problems like insomnia traits in ASD. We investigated the contribution of copy number variants (CNVs) encompassing circadian pathway genes and insomnia risk genes to ASD risk as well as sleep disturbances in children with ASD. We studied 5860 ASD probands and 2092 unaffected siblings from the Simons Simplex Collection (SSC) and MSSNG database, as well as 7509 individuals from two unselected populations (IMAGEN and Generation Scotland). Sleep duration and insomnia symptoms were parent reported for SSC probands. We identified 335 and 616 rare CNVs encompassing circadian and insomnia risk genes respectively. Deletions and duplications with circadian genes were overrepresented in ASD probands compared to siblings and unselected controls. For insomnia-risk genes, deletions (not duplications) were associated with ASD in both cohorts. Results remained significant after adjusting for cognitive ability. CNVs containing circadian pathway and insomnia risk genes showed a stronger association with ASD, compared to CNVs containing other genes. Circadian genes did not influence sleep duration or insomnia traits in ASD. Insomnia risk genes intolerant to haploinsufficiency increased risk for insomnia when duplicated. CNVs encompassing circadian and insomnia risk genes increase ASD liability with little to no observable impacts on sleep disturbances.

Domaines: Psychiatrie et santé mentale; Génétique humaine; Génétique des populations [q-bio.PE]

Rackeb Tesfaye, Guillaume Huguet, Zoe Schmilovich, Thomas Renne, Mor Absa Loum, et al.. Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances. Translational Psychiatry, 2022, 12 (1), pp.424. ⟨10.1038/s41398-022-02188-2⟩. ⟨hal-04542946⟩