TY - JOUR
T1 - Common and rare variants of microRNA genes in autism spectrum disorders
AU - Toma, Claudio
AU - Torrico, Bàrbara
AU - Hervás, Amaia
AU - Salgado, Marta
AU - Rueda, Isabel
AU - Valdés-Mas, Rafael
AU - Buitelaar, Jan K.
AU - Rommelse, Nanda
AU - Franke, Barbara
AU - Freitag, Christine
AU - Reif, Andreas
AU - Pérez-Jurado, Luis Alberto
AU - Battaglia, Agatino
AU - Mazzone, Luigi
AU - Bacchelli, Elena
AU - Puente, Xose S.
AU - Cormand, Bru
PY - 2015/8/18
Y1 - 2015/8/18
N2 - 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.
AB - 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.
KW - autistic disorder
KW - biological psychiatry
KW - exome
KW - genetic association studies
KW - MicroRNAs
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U2 - 10.3109/15622975.2015.1029518
DO - 10.3109/15622975.2015.1029518
M3 - Article
AN - SCOPUS:84941616414
SN - 1562-2975
VL - 16
SP - 376
EP - 386
JO - World Journal of Biological Psychiatry
JF - World Journal of Biological Psychiatry
IS - 6
ER -