Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility.

Objectives: MicroRNAs (miRNAs) play an important regulatory role in the expression of genes involved in brain functions during development. Genetic variants in miRNA genes may impact their regulatory function and lead to psychiatric disorders. To evaluate the role of genetic variants in genes of miRNAs differentially expressed during neurodevelopment on autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD).

Methods: The miRNAs were identified in the literature. Summary statistics from the most recent genome-wide association studies to date were used to evaluate the association between the selected polymorphisms and each disorder in a look-up approach. In a global analysis, we compared the standardised risk effect of variants in neurodevelopment-related miRNAs with those in the remaining miRNAs from miRBase.

Results: The global analysis showed that variants in neurodevelopment-related miRNAs had higher risk effects compared to the other miRNAs for SCZ ( = 0.010) and ADHD ( = 0.001). , , and were significantly associated with SCZ, while 55.9% of the miRNAs were at least nominally associated with one or more psychiatric disorders ( < 0.05).

Conclusions: Genetic variants in neurodevelopment-related miRNAs play an important role in the genetic susceptibility of psychiatric disorders, mainly SCZ and ADHD.