RT Journal Article
SR Electronic
T1 Investigation of the involvement of <em>MIR185</em> and its target genes in the development of schizophrenia
JF Journal of Psychiatry and Neuroscience
JO J Psychiatry Neurosci
FD Canadian Medical Association
SP 386
OP 396
DO 10.1503/jpn.130189
VO 39
IS 6
A1 Andreas J. Forstner
A1 F. Buket Basmanav
A1 Manuel Mattheisen
A1 GROUP Investigators
A1 Anne C. Böhmer
A1 Mads V. Hollegaard
A1 Esther Janson
A1 Eric Strengman
A1 Lutz Priebe
A1 Franziska Degenhardt
A1 Per Hoffmann
A1 Stefan Herms
A1 Wolfgang Maier
A1 Rainald Mössner
A1 Dan Rujescu
A1 Roel A. Ophoff
A1 Susanne Moebus
A1 Preben B. Mortensen
A1 Anders D. Børglum
A1 David M. Hougaard
A1 Josef Frank
A1 Stephanie H. Witt
A1 Marcella Rietschel
A1 Andreas Zimmer
A1 Markus M. Nöthen
A1 Xavier Miró
A1 Sven Cichon
YR 2014
UL http://jpn.ca/content/39/6/386.abstract
AB Background: Schizophrenia is a complex neuropsychiatric disorder of unclear etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion. Research has yet to confirm which genes within the deletion region are implicated in schizophrenia. The minimal 1.5 megabase deletion contains MIR185, which encodes microRNA 185.Methods: We determined miR-185 expression in embryonic and adult mouse brains. Common and rare variants at this locus were then investigated using a human genetics approach. First, we performed gene-based analyses for MIR185 common variants and target genes using Psychiatric Genomics Consortium genome-wide association data. Second, MIR185 was resequenced in German patients (n = 1000) and controls (n = 500). We followed up promising variants by genotyping an additional European sample (patients, n = 3598; controls, n = 4082).Results: In situ hybridization in mice revealed miR-185 expression in brain regions implicated in schizophrenia. Gene-based tests revealed association between common variants in 3 MIR185 target genes (ATAT1, SH3PXD2A, NTRK3) and schizophrenia. Further analyses in mice revealed overlapping expression patterns for these target genes and miR-185. Resequencing identified 2 rare patient-specific novel variants flanking MIR185. However, follow-up genotyping provided no further evidence of their involvement in schizophrenia.Limitations: Power to detect rare variant associations was limited.Conclusion: Human genetic analyses generated no evidence of the involvement of MIR185 in schizophrenia. However, the expression patterns of miR-185 and its target genes in mice, and the genetic association results for the 3 target genes, suggest that further research into the involvement of miR-185 and its downstream pathways in schizophrenia is warranted.