Common and rare variants of microRNA genes in autism spectrum disorders

Claudio Toma, Bàrbara Torrico, Amaia Hervás, Marta Salgado, Isabel Rueda, Rafael Valdés-Mas, Jan K. Buitelaar, Nanda Rommelse, Barbara Franke, Christine Freitag, Andreas Reif, Luis Alberto Pérez-Jurado, Agatino Battaglia, Luigi Mazzone, Elena Bacchelli, Xose S. Puente, Bru Cormand

Research output: Contribution to journalArticlepeer-review


Objectives. MicroRNAs (miRNAs) are post-transcriptional regulators that have been shown to be involved in disease susceptibility. Here we explore the possible contribution of common and rare variants in miRNA genes in autism spectrum disorders (ASD). Methods. A total of 350 tag SNPs from 163 miRNA genes were genotyped in 636 ASD cases and 673 controls. A replication study was performed in a sample of 449 ASD cases and 415 controls. Additionally, rare variants in 701 miRNA genes of 41 ASD patients were examined using whole-exome sequencing. Results. The most significant association in the discovery sample was obtained for the miR-133b/miR-206 cluster (rs16882131, P = 0.00037). The replication study did not reach significance. However, the pooled analysis (1,085 cases and 1,088 controls) showed association with two miRNA clusters: miR-133b/miR-206 (rs16882131, permP = 0.037) and miR-17/miR-18a/miR-19a/miR-20a/miR-19b-1/miR92a-1 (rs6492538, permP = 0.019). Both miR-133b and miR-206 regulate the MET gene, previously associated with ASD. Rare variant analysis identified mutations in several miRNA genes, among them miR-541, a brain-specific miRNA that regulates SYN1, found mutated in ASD. Conclusions. Although our results do not establish a clear role for miRNAs in ASD, we pinpointed a few candidate genes. Further exome and GWAS studies are warranted to get more insight into their potential contribution to the disorder.

Original languageEnglish
Pages (from-to)376-386
Number of pages11
JournalWorld Journal of Biological Psychiatry
Issue number6
Publication statusPublished - Aug 18 2015


  • autistic disorder
  • biological psychiatry
  • exome
  • genetic association studies
  • MicroRNAs

ASJC Scopus subject areas

  • Biological Psychiatry
  • Psychiatry and Mental health


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