Shared predicted effector genes of insomnia, anxiety and depression implicate synaptic processes as transdiagnostic drug targets

Insomnia, depression, and anxiety share 55% of their GWAS signal, with 195 cross-disorder loci converging on shared predicted effector genes tied to synaptic biology.

• Why it matters: Shared genetic vulnerability across these co-occurring conditions could reveal mechanisms that are actionable for transdiagnostic drug development, addressing gaps in current clinical care.
• What they did: Using a multi-level trivariate GWAS framework, the study assessed trivariate overlap, local genetic correlations, shared genome-wide loci, shared predicted effector genes, and shared putative causal variants.
• The result: Many loci likely reflect the same causal variant (at least 50%) or predicted effector gene (60–80%), implicating inhibitory synaptic transmission and nominating CACNA2D3, DRD2, GRIA1, and GRM5 as drug targets.

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