The Genomic Locus Can Affect Treatment of Psychiatric Illness Through Gene Expression Changes Related to MicroRNA-484

Overview

Journal Open Biol

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Nov 17

PMID 29142105

Citations 9

Authors

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 Lonnqvist

Tyrone D Cannon

Jari Haukka

William Hennah

Affiliations

Soon will be listed here.

Abstract

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, , , , and , 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 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 ( = 3.0 × 10), located on a non-coding exon of Variants within the 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 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.

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