No effect of genome-wide significant schizophrenia risk variation at the DRD2 locus on the allelic expression of DRD2 in post-mortem striatum

Toste, Carolina, Duarte, Rodigo, Jeffries, Aaron, Selvackadunco, Sashika, Troakes, Claire, O'Donovan, Michael ORCID: https://orcid.org/0000-0001-7073-2379, Hill, Matthew ORCID: https://orcid.org/0000-0001-6776-8709 and Bray, Nicholas ORCID: https://orcid.org/0000-0002-4357-574X 2019. No effect of genome-wide significant schizophrenia risk variation at the DRD2 locus on the allelic expression of DRD2 in post-mortem striatum. Molecular Neuropsychiatry 5 (4) , pp. 212-217. 10.1159/000501022

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Abstract

A genome-wide significant association has been reported between non-coding variants at the dopamine D2 receptor (DRD2) gene locus and schizophrenia. However, effects of identified schizophrenia risk alleles on DRD2 function are yet to be demonstrated. Using highly sensitive measures of allele-specific expression, we have assessed cis-regulatory effects associated with genotype at lead SNP rs2514218 on DRD2expression in the adult human striatum. No significant differences were observed in the extent of allelic expression imbalance between samples that were genomic heterozygotes for rs2514218 (where cis-regulatory effects of the risk allele are compared with those of the non-risk allele within individual subjects) and samples that were homozygous for rs2514218 (where cis-regulatory effects of this SNP on each expressed DRD2 allele will be equal). We therefore conclude that rs2514218 genotype is not associated with large effects on overall DRD2 RNA expression, at least in postmortem adult striatum. Alternative explanations for the genetic association between this variant and schizophrenia include effects on DRD2 that are transcript specific, restricted to minor DRD2-expressing cell populations or elicited only under certain physiological circumstances, or mediation through effects on another gene (or genes) at the locus.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	Karger Publishers
ISSN:	2296-9209
Funders:	MRC
Date of First Compliant Deposit:	23 May 2019
Date of Acceptance:	16 May 2019
Last Modified:	26 Jul 2024 16:00
URI:	https://orca.cardiff.ac.uk/id/eprint/122793

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