Table 1.
Variants in miRNA genes in neuropsychiatric disorders.
| MiRNA | Population | Number of samples | Functional result | |
|---|---|---|---|---|
| Hansen et al. (2007) | SNP in miR-198 (rs1700) and miR-206 (rs17578796) |
Scandinavian | Danish subjects: 420 SCZ patients, 1006 control subjects Norwegian subjects: 257 SCZ patients, 293 control subjects Swedish subjects: 163 SCZ patients, 177 control subjects |
One pathway was identified with 8 common targets to both miRNAs (PTPN, CCND2, CREB5, MET, N-PAC, MEIS1, PUM2.AP1G1) |
| Burmistrova et al. (2007) | SNP in miR-130b (rs861843) | Russian | 300 SCZ patients, 316 control subjects | Not assessed |
| Feng et al. (2009) | SNP in miR-188, miR-18b/18b*, miR-502, miR-505, miR-510, miR-660, miR-325, miR-509-3, let-7f-2 |
Caucasian | 193 SCZ patients, 191 control subjects | CLCN5, HMGA2, NRXN3, DISCI, NRG1, MECP2, RGS4, GRM3, ERBB4, MAGI2, DLG2 |
|
Xu et al. (2010) Schizophrenia Psychiatric Genome-Wide Association Study (2011) |
SNP in pre-miR-30e (ss178077483) SNP in miR-137 (rs1625579) |
Chinese Genome-Wide Association Study |
456 SCZ patients, 453 control subjects 17,836 SCZ patients, 33,859 control subjects |
Ubc9 Implicated in regulation of adult neurogenesis and neuronal maturation. Four predicted targets (TCF4, CACNA1C, CSMD and C10orf26) were found to have SNPs associated with schizophrenia |
|
Whalley et al. (2012) Begemann et al. (2010) |
SNP in miR-137 (rs1625579) SNP in miR-498 (rs3822674) |
Scottish Caucasian, 95.3%; other, 1.6%; unknown, 3.1%) |
44 high genetic risk of SCZ, 81 controls 792 SCZ patients, 159 patients with schizoaffective disorder, 120 suspected schizophrenic psychosis cases, 1079 control subjects |
Not assessed 3′UTR of candidate schizophrenia genes, a SNP in the complexin 2 (CPLX2) 3′UTR in a predicted binding site of miR-498. |
| Green et al. (2013) | SNP in miR-137 (rs1625579) | Australian | 526 SCZ patients, 91 patients with schizoaffective disorder, 764 control subjects |
Not assessed |
| Cummings et al. (2013) | SNP in mir-137 (rs1625579) | Irish | 821 SCZ patients, BD patients and schizoaffective disorder, 171 control subjects |
Associated with a specific psychosis phenotype. |
| Ripke et al. (2013) | SNP in miR-137 (rs1198588) | Swedish | 5001 SCZ patients, 6243 control subjects | The SNP with the strongest association to schizophrenia (rs1198588) is 39 kb upstream of MIR137, and might regulate the transcription of MIR137. |
| Psychosis Endophenotypes International et al. (2014) | SNP in miR-137 (rs1702294) and miR-548aj2(rs215411) |
Genome-Wide Association Study |
36,989 SCZ patients, 113,075 control subjects | Not assessed |
| Warnica et al. (2015) | CNVs at eight loci: Iq21.1, 2q13, 12q21.31, 14q32.33, 15q11-15q13, 16p11.2, 16p13.11, and 19q13.42 |
Canadian | 420 SCZ patients, 2357 control subjects | Predicted gene targets: CAPRIN1, NEDD4, NTRK2, PAK2, RHOA, and SYNGAP1 |
| Whalley et al. (2012) | SNP in miR-137 (rs1625579) | Scottish | 90 high genetic risk of BD, 81 control subjects | Not assessed |
| Forstner et al. (2015) | SNPs in miR-199, miR-640, miR-708, miR-581, miR-644, miR-135a-1, miR-1908, let-7g |
Genome-Wide Association Study |
9747 BD patients, 14,278 controls | Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. |
| Saus et al. (2010a,b) | SNP in pre-mir-182 (rs76481776) | Spanish | 359 MDD patients, 341 control subjects | Associated with late insomnia in MDD. |
| Xu et al. (2010) | SNP in pre-miR-30e (ss178077483) | Chinese | 1088 MDD patients, 1102 control subjects | Not assessed |
|
Variants in miRNA target genes in neuropsychiatric disorders | ||||
| SNP/CNV | Population | Number of samples | Functional result | |
| Begemann et al. (2010) | SNP in CPLX2 gene (affecting miR-498 binding) (rs3822674) |
Caucasian | 1071 SCZ patients, 1079 control subjects | CPLX2 gene is associated with altered cognition in SCZ patients. |
| Gong et al. (2013) | SNPs in GABRA6 (rs3219151), COMT (rs165599) and RCS4 (rs10759) (affecting miR-124 binding) |
Chinese | 598 SCZ patients, 500 control subjects | In vitro luciferase assays demonstrated that regulator of G-protein signaling 4 (RGS4) downregulation was mediated by miR-124, and that miR-124 binding can be modified by SNP rs10759. |
| Liu et al. (2012) | SNPs in TBCW15 gene (rs17110432, rs11178988, rs11178989) possibly affecting miRNA binding |
Chinese | 746 SCZ patients, 1599 control subjects | Not assessed |
| Kandaswamy et al. (2014) | SNP in CRM7 gene (rs56173829) predicted to differential miRNA binding. |
British | 553 BD patients and 547 control subjects | Bioinformatic analyses predicted a change in the centroid secondary structure of RNA and alterations in the miRNA binding sites for the mutated base of rs56173829. |
| Rahman et al. (2010) | SNP in predicted binding site of miR-625 and miR-1302 in P2RX7 gene (rs1653625l |
Unspecified | 171 MDD or BD patients, 178 control subjects | P2RX7 |
| Jensen et al. (2014) |
SNPs: Predicted binding site of miR-330-3p in MAP2K5 gene; only significant in African Americans (rs41305272) |
European Americans: 465 cases, 2010 controls African Americans: 427 cases, 2584 controls |
314 MDD patients, 252 control subjects | MAP2K5. Enriched pathways include TGF, WNT and cytoskeletal remodeling, neurotrophin family signaling, roles of HDAC and CaMK in control of skeletal myogenesis, nervous system development, system development, neurogenesis, axonal guidance, FSH-beta signaling pathway, FGF-ErbB signaling. Genes involved in mental disorders, psychiatry and psychology, and schizophrenia. |
|
Variants in miRNA biogenesis genes in neuropsychiatric disorders | ||||
| Gene | Population | Number of samples | Functional result | |
| Beveridge et al. (2010) | Upregulation: DGCR8 (miRNA biogenesis gene) |
Caucasian | 21 SCZ patients, 21 control subjects |
Upregulation of the microprocessor component DGCR8 mRNA; related to an increase of both mature miRNA and precursor forms of miR-181b and miR-26b |
| Santarelli et al. (2011) | Upregulation: Confirmed by qPCR: Dicer (miRNA biogenesis gene) |
Caucasian | 37 cases (SCZ or schizoaffective disorder), 37 control subjects |
|
| Zhou et al. (2013) | Two polymorphisms in the DGCR8 and DICER genes (rs3757 and rs3742330) |
Chinese | 255 SCZ patients, 252 control subjects | Polymorphisms in two miRNA machinery genes, functional significance of these variants is, as yet, undetermined. |
| Smalheiser et al. (2012) | No significant differences were found in Dicer, Drosha and DGCR8 mRNAs (miRNA biogenesis gene). |
Unspecified | 18 MDD, 17 controls | Not assessed |
| He et al. (2012) | SNPs: DGCR8 (miRNA biogenesis gene) (rs3757), AGOl (RISC component) (rs636832) |
Chinese | 314 MDD, 252 controls | Not assessed |