Genetic architecture and polygenic prediction of self-reported response to selective serotonin reuptake inhibitors in individuals with depression: a genome-wide meta-analysis

In 62,879 European-ancestry individuals with depression, self-reported SSRI response shows modest SNP heritability (h2 = 3.1%, SE = 1.4%) but no genome-wide significant variants.

• Why it matters: SSRI outcomes vary widely, yet robust genetic predictors are lacking; this work targets the missing link between depression genetics and patient-reported treatment response.
• What they did: They ran a genome-wide association meta-analysis across six cohorts (seven datasets), then performed gene-set, transcriptomic, proteomic, drug-target, and leave-one-out polygenic score analyses.
• The result: A leave-one-out PGS from discovery predicted self-reported response in independent cohorts (meta-analysis OR = 1.05, 95% CI 1.02--1.08, p = 0.002), while higher psychiatric-condition PGS predicted lower response and educational attainment PGS predicted better response.

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