Genome-wide association study and polygenic risk score analysis of esketamine treatment response
Scientific Reports July 28, 2020 Qingqin S. Li, Ewa Wajs, Rachel Ochs-Ross et al. 49 citations
A genome-wide association study in 527 people of European ancestry with major depressive disorder identified a significant genetic locus in the IRAK3 gene and a significant gene-level association in NME7 linked to the antidepressant efficacy of esketamine nasal spray, measured as percentage change in symptom severity. Polygenic risk score analysis showed the strongest association with esketamine efficacy came from genetic loading for depressive symptoms, though this did not reach study-wide significance. Suggestive signals were enriched in pathways related to neuronal and synaptic function, immune signaling, and glucocorticoid receptor/stress response.