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Altered expression of lncRNAs in autism spectrum disorder

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Abstract

Long non-coding RNAs (lncRNAs) have been recognized as an important epigenetic factor in the evolution of neuropsychiatric conditions. We have selected five lncRNAs (DISC2, PRKAR2A-AS1, LOC105375675, LRRC2-AS1, and LOC101928237) to measure their expression in blood samples of children with autism spectrum disorder (ASD) versus children with normal development. Expressions of DISC2, PRKAR2A-AS1 and LOC101928237 have been enhanced in ASD cases compared with healthy children (Posterior Beta = 2.508, P value<0.0001; Posterior Beta = 2.793, P value = 0.014 and Posterior Beta = 1.646, P value <0.0001, respectively). On the other hand, expression of LRRC2-AS1 has been lower in ASD patients compared with controls (Posterior Beta = −3.781, P value<0.0001). Remarkably, expression of DISC2 and PRKAR2A-AS1 have been lower in girls compared with boys (Posterior Beta = −0.982, P value<0.0001 and Posterior Beta = −0.135, P value<0.0001, respectively). In addition, expression of DISC2 has been lower in ASD cases aged more than 6 compared with those aged less than 6 years (Posterior Beta = −0.876, P value = 0.003). DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 had the area under curve (AUC) values of 0.76, 0.90, 0.92, and 0.79 in distinguishing between ASD and healthy children. Expression levels of none of DISC2, LOC101928237, LOC105375675, LRRC2-AS1, and PRKAR2A-AS1 were correlated with age of ASD cases or healthy controls. A significant correlation was detected between expressions of DISC2 and PRKAR2A-AS1. There were inverse correlations between the following pairs of lncRNAs: DISC2/LRRC2-AS1, DISC2/LOC101928237, LRRC2-AS1/PRKAR2A-AS1, LOC101928237/LRRC2-AS1, and LOC101928237 /LOC105375675. We conclude that DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 might be used as potential markers for this condition.

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Data availability

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was financially supported by Shahid Beheshti University of Medica Sciences.

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KH and MDO performed the experiment. FP and SAJ analyzed the data. MT and SGF designed the study and wrote the draft and revised it. All the authors contribute equally and read the submission.

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Correspondence to Soudeh Ghafouri-Fard or Mohammad Taheri.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent forms were obtained from all study participants. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1399.14). All methods were performed in accordance with the relevant guidelines and regulations.

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Tamizkar, K.H., Ghafouri-Fard, S., Omrani, M.D. et al. Altered expression of lncRNAs in autism spectrum disorder. Metab Brain Dis 36, 983–990 (2021). https://doi.org/10.1007/s11011-021-00681-z

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