Altered expression of lncRNAs in autism spectrum disorder.

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 6years (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.