Association study of phosphodiesterase genes in the Sequenced Treatment Alternatives to Relieve Depression sample

Abstract

A recent study has reported a significant association of variants in phosphodiesterase (PDE) genes with antidepressant treatment outcome in a Mexican American sample. We set out to investigate these findings in a large sample of patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. STAR*D is a longitudinal study of antidepressant outcome in depressed outpatients. We genotyped three single nucleotide polymorphisms (SNPs) in PDE11A (rs1880916), PDE1A (rs1549870), and PDE9A (rs729861) for replication and we also report three additional SNPs in PDE11A (rs3770016, rs4893975, rs6433687) that had been genotyped for a previous study. Single marker analysis of remission within the Hispanic subsamples (n=268) revealed no significant evidence of association with markers in PDE11A, PDE9A, or PDE1A. Additional analyses of remission within the total STAR*D sample (n=1914) were also largely negative, as were analyses utilizing a narrower definition of remission. Haplotype analyses were carried out with the four PDE11A SNPs we genotyped; these also failed to show significant evidence of association in the STAR*D sample. In conclusion, we could not reproduce the reported association between PDE genes and antidepressant outcome in a sample of participants comparable to that reported previously. We conclude that PDE11A, PDE9A, and PDE1A are unlikely to play an important role in antidepressant outcome in this sample.