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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 DRD2 expression 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.

complex psychiatry

No Effect of Genome-Wide Significant Schizophrenia Risk Variation at the &lt;b&gt;&lt;i&gt;DRD2&lt;/i&gt;&lt;/b&gt; Locus on the Allelic Expression of &lt;b&gt;&lt;i&gt;DRD2&lt;/i&gt;&lt;/b&gt; in Postmortem Striatum