The non-synonymous P2RX7 SNP rs2230912 is associated with affective disorders: Results from an association study in major depression and from a meta-analysis

Since the first report of an association of SNPs in the P2RX7 gene with bipolar disorder (BD) eight subsequent studies have been published testing associations of the non-synonymous P2RX7 SNP rs2230912 with BD and/or major depressive disorder (MDD). While three studies reported association of this SNP, other studies did not detect significant associations. P2RX7 encodes a brain-expressed receptor, is involved in Ca²⁺ dependent signal pathways and may regulate immune function and neurotransmitter release. We tested rs2230912 for association with MDD in the Munich Antidepressant Response Signature (MARS) study (543 depressed patients versus 542 control subjects) and performed a meta-analysis taking into account the eight published studies as well as the additional ninth study. In our association study with MDD a nominally significant association was observed for rs2230912 for the genotypic and the allelic (nominal p = 0.0251) but not for the dominant or heterozygous-disadvantage model. The association did not withhold correction for testing different modes of inheritance. The meta-analysis however resulted in a significant effect of rs2230912 on MDD/BD case-control status in the heterozygous-disadvantage model (p = 0.0028). This effect is significant after correction for multiple testing. Our association study and the meta-analysis thus further point towards a possible causal role of the non-synonymous P2RX7 SNP rs2230912 in affective disorders.