Brain Expressed microRNAs Implicated in Schizophrenia Etiology.

@article{citeulike:1652577, abstract = {BACKGROUND: Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the association between schizophrenia and genetic variants of miRNA genes associated with brain-expression using a case-control study design on three Scandinavian samples. Eighteen known SNPs within or near brain-expressed miRNAs in three samples (Danish, Swedish and Norwegian: 420/163/257 schizophrenia patients and 1006/177/293 control subjects), were analyzed. Subsequently, joint analysis of the three samples was performed on SNPs showing marginal association. Two SNPs rs17578796 and rs1700 in hsa-mir-206 (mir-206) and hsa-mit-198 (mir-198) showed nominal significant allelic association to schizophrenia in the Danish and Norwegian sample respectively (P = 0.0021 \& p = 0.038), of which only rs17578796 was significant in the joint sample. In-silico analysis revealed that 8 of the 15 genes predicted to be regulated by both mir-206 and mir-198, are transcriptional targets or interaction partners of the JUN, ATF2 and TAF1 connected in a tight network. JUN and two of the miRNA targets (CCND2 and PTPN1) in the network have previously been associated with schizophrenia. CONCLUSIONS/SIGNIFICANCE: We found nominal association between brain-expressed miRNAs and schizophrenia for rs17578796 and rs1700 located in mir-206 and mir-198 respectively. These two miRNAs have a surprising large number (15) of targets in common, eight of which are also connected by the same transcription factors.}, address = {Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.}, author = {Hansen, Thomas and Olsen, Line and Lindow, Morten and Jakobsen, Klaus D D. and Ullum, Henrik and Jonsson, Erik and Andreassen, Ole A A. and Djurovic, Srdjan and Melle, Ingrid and Agartz, Ingrid and Hall, H\r{a}kan and Timm, Sally and Wang, August G G. and Werge, Thomas }, citeulike-article-id = {1652577}, doi = {10.1371/journal.pone.0000873}, issn = {1932-6203}, journal = {PLoS ONE}, keywords = {brain, mirna, schizophrenia}, number = {9}, posted-at = {2007-09-13 19:12:44}, priority = {2}, title = {Brain Expressed microRNAs Implicated in Schizophrenia Etiology.}, url = {http://dx.doi.org/10.1371/journal.pone.0000873}, volume = {2}, year = {2007} }

TY - JOUR ID - citeulike:1652577 L3 - citeulike-article-id:1652577 TI - Brain Expressed microRNAs Implicated in Schizophrenia Etiology. JF - PLoS ONE VL - 2 IS - 9 AD - Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark. SN - 1932-6203 N2 - BACKGROUND: Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the association between schizophrenia and genetic variants of miRNA genes associated with brain-expression using a case-control study design on three Scandinavian samples. Eighteen known SNPs within or near brain-expressed miRNAs in three samples (Danish, Swedish and Norwegian: 420/163/257 schizophrenia patients and 1006/177/293 control subjects), were analyzed. Subsequently, joint analysis of the three samples was performed on SNPs showing marginal association. Two SNPs rs17578796 and rs1700 in hsa-mir-206 (mir-206) and hsa-mit-198 (mir-198) showed nominal significant allelic association to schizophrenia in the Danish and Norwegian sample respectively (P = 0.0021 & p = 0.038), of which only rs17578796 was significant in the joint sample. In-silico analysis revealed that 8 of the 15 genes predicted to be regulated by both mir-206 and mir-198, are transcriptional targets or interaction partners of the JUN, ATF2 and TAF1 connected in a tight network. JUN and two of the miRNA targets (CCND2 and PTPN1) in the network have previously been associated with schizophrenia. CONCLUSIONS/SIGNIFICANCE: We found nominal association between brain-expressed miRNAs and schizophrenia for rs17578796 and rs1700 located in mir-206 and mir-198 respectively. These two miRNAs have a surprising large number (15) of targets in common, eight of which are also connected by the same transcription factors. KW - brain KW - mirna KW - schizophrenia AU - Hansen, Thomas AU - Olsen, Line AU - Lindow, Morten AU - Jakobsen, Klaus D AU - Ullum, Henrik AU - Jonsson, Erik AU - Andreassen, Ole A AU - Djurovic, Srdjan AU - Melle, Ingrid AU - Agartz, Ingrid AU - Hall, Håkan AU - Timm, Sally AU - Wang, August G AU - Werge, Thomas PY - 2007/// UR - http://dx.doi.org/10.1371/journal.pone.0000873 ER -