The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484
Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the ‘DISC1 network’. Here, we use gene expression and psychoactive medication use data to study their biological consequences a...
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doaj-4b629c90c56d4cd896a19d72e6ebdeb42020-11-25T01:19:28ZengThe Royal SocietyOpen Biology2046-24412017-01-0171110.1098/rsob.170153170153The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484Nicholas J. BradshawLiisa Ukkola-VuotiMaiju PankakoskiAmanda B. ZheutlinAlfredo Ortega-AlonsoMinna Torniainen-HolmVishal SinhaSebastian ThermanTiina PaunioJaana SuvisaariJouko LönnqvistTyrone D. CannonJari HaukkaWilliam HennahGenetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the ‘DISC1 network’. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10−8), located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170153schizophreniagene expressiondisc1 networknde1mir-484pharmacogenetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicholas J. Bradshaw Liisa Ukkola-Vuoti Maiju Pankakoski Amanda B. Zheutlin Alfredo Ortega-Alonso Minna Torniainen-Holm Vishal Sinha Sebastian Therman Tiina Paunio Jaana Suvisaari Jouko Lönnqvist Tyrone D. Cannon Jari Haukka William Hennah |
spellingShingle |
Nicholas J. Bradshaw Liisa Ukkola-Vuoti Maiju Pankakoski Amanda B. Zheutlin Alfredo Ortega-Alonso Minna Torniainen-Holm Vishal Sinha Sebastian Therman Tiina Paunio Jaana Suvisaari Jouko Lönnqvist Tyrone D. Cannon Jari Haukka William Hennah The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484 Open Biology schizophrenia gene expression disc1 network nde1 mir-484 pharmacogenetics |
author_facet |
Nicholas J. Bradshaw Liisa Ukkola-Vuoti Maiju Pankakoski Amanda B. Zheutlin Alfredo Ortega-Alonso Minna Torniainen-Holm Vishal Sinha Sebastian Therman Tiina Paunio Jaana Suvisaari Jouko Lönnqvist Tyrone D. Cannon Jari Haukka William Hennah |
author_sort |
Nicholas J. Bradshaw |
title |
The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484 |
title_short |
The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484 |
title_full |
The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484 |
title_fullStr |
The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484 |
title_full_unstemmed |
The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484 |
title_sort |
nde1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microrna-484 |
publisher |
The Royal Society |
series |
Open Biology |
issn |
2046-2441 |
publishDate |
2017-01-01 |
description |
Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the ‘DISC1 network’. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10−8), located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment. |
topic |
schizophrenia gene expression disc1 network nde1 mir-484 pharmacogenetics |
url |
https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170153 |
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