Genome-wide association studies of placebo and duloxetine response in major depressive disorder.
Pharmacogenomics J
; 18(3): 406-412, 2018 05 22.
Article
in En
| MEDLINE
| ID: mdl-28696415
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 (ß=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; ß=-0.46, P=1.55 × 10-5), NCAM1 (rs2303377; ß=0.45, P=1.76 × 10-5) and MLL5 (rs117986340; ß=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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Depressive Disorder, Major
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DNA-Binding Proteins
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Genome-Wide Association Study
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Nerve Tissue Proteins
Type of study:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Pharmacogenomics J
Journal subject:
BIOLOGIA MOLECULAR
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FARMACOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
Canada