title: Common and rare variants of microRNA genes in autism spectrum disorders.
abstract: OBJECTIVE
  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.
authors.affiliation: a Departament de Genètica, Universitat de Barcelona , Spain.|b Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Spain.
authors.forename: Claudio
authors.initials: C
authors.lastname: Toma
authors.affiliation: a Departament de Genètica, Universitat de Barcelona , Spain.|b Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Spain.
authors.forename: Bàrbara
authors.initials: B
authors.lastname: Torrico
authors.affiliation: c Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa , Spain.|d Developmental Disorders Unit (UETD), Hospital Sant Joan de Déu, Esplugues de Llobregat , Barcelona , Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Hervás
authors.affiliation: c Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa , Spain.|d Developmental Disorders Unit (UETD), Hospital Sant Joan de Déu, Esplugues de Llobregat , Barcelona , Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Salgado
authors.affiliation: d Developmental Disorders Unit (UETD), Hospital Sant Joan de Déu, Esplugues de Llobregat , Barcelona , Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rueda
authors.affiliation: e Department of Biochemistry and Molecular Biology , University of Oviedo-IUOPA , Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Valdés-Mas
authors.affiliation: f Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience , Nijmegen , The Netherlands.|g Karakter Child and Adolescent Psychiatry University Centre , Nijmegen , The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: g Karakter Child and Adolescent Psychiatry University Centre , Nijmegen , The Netherlands.|h Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry , Nijmegen , The Netherlands.
authors.forename: Nanda
authors.initials: N
authors.lastname: Rommelse
authors.affiliation: h Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry , Nijmegen , The Netherlands.|i Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics , Nijmegen , The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: j Department of Psychiatry , Psychosomatic Medicine and Psychotherapy, University Hospital , Frankfurt , Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Freitag
authors.affiliation: k Department of Psychiatry , Psychosomatics, and Psychotherapy, University of Wuerzburg , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: b Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Spain.|l Unitat de Genètica, Universitat Pompeu Fabra , Barcelona , Spain.|m Hospital del Mar Research Institute, IMIM , Barcelona , Spain.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Pérez-Jurado
authors.affiliation: n Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry , Calambrone, Pisa , Italy.
authors.forename: Agatino
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: o Child Neuropsychiatry Unit, Department of Neuroscience , I.R.C.C.S. Children's Hospital Bambino Gesù , Rome , Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Mazzone
authors.affiliation: p Department of Pharmacy and Biotechnology , University of Bologna , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bacchelli
authors.affiliation: e Department of Biochemistry and Molecular Biology , University of Oviedo-IUOPA , Spain.
authors.forename: Xose S
authors.initials: XS
authors.lastname: Puente
authors.affiliation: a Departament de Genètica, Universitat de Barcelona , Spain.|b Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Spain.|q Institut de Biomedicina de la Universitat de Barcelona (IBUB) , Spain.
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
keywords: MicroRNAs; autistic disorder; biological psychiatry; exome; genetic association studies