Genome-wide association studies of placebo and duloxetine response in major depressive disorder

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Abstract

We investigated variants associated with treatment response in depressed patients treated with either the antidepressant duloxetine or placebo using a genome-wide approach. Our sample (N = 391) included individuals aged 18-75 years, diagnosed with major depressive disorder and treated with either duloxetine or placebo for up to 8 weeks. We conducted genome-wide associations for treatment response as operationalized by percentage change in Montgomery-Åsberg Depression Rating Scale score from baseline, as well as mixed models analyses across five time points. In the placebo-treated subsample (N = 205), we observed a genome-wide association with rs76767803 (β = 0.69, P = 1.25 × 10− 8) upstream of STAC1. STAC1 rs76767803 was also associated with response using mixed model analysis (χ2 = 3.95; P = 0.001). In the duloxetine-treated subsample (N = 186), we observed suggestive associations with ZNF385D (rs4261893; β = − 0.46, P = 1.55 × 10− 5), NCAM1 (rs2303377; β = 0.45, P = 1.76 × 10− 5) and MLL5 (rs117986340; β = 0.91, P = 3.04 × 10− 5). Our findings suggest that a variant upstream of STAC1 is associated with placebo response, which might have implications for treatment optimization, clinical trial design and drug development.

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