Unveiling Shared Heritability in Psychiatric Disorders: Insights from Recent Genomic Studies

A large genomics meta-analysis suggests five genetic families account for most shared heritable risk across 14 psychiatric disorders, pointing to transdiagnostic biomarkers and potential diagnostic refinement.

The team combined genome-wide summary data across 14 disorders, applied factor analysis and locus-level mapping, and found that five broad genetic factors explain roughly two-thirds of SNP heritability.

The five genetic factors map to clinically meaningful clusters: mood–internalizing (major depression, anxiety, PTSD), psychosis–spectrum (schizophrenia, bipolar presentations), neurodevelopmental (autism spectrum disorder, ADHD, Tourette’s), compulsive/obsessive traits (anorexia nervosa, OCD), and substance-use/impulsivity (alcohol, cannabis, opioid, nicotine dependence plus impulsive traits). These families capture the bulk of shared polygenic risk across the disorders.

According to the analysis, shared genetic factors were enriched in particular neuronal classes and in prenatal-to-early-postnatal developmental windows; those results derive from cell-type enrichment and developmental-expression analyses in the underlying study.

Locus-level discovery identified 238 associated loci, with many loci mapping to multiple factors and a smaller subset appearing disorder-specific. Shared versus disorder-specific signals were defined by factor loadings across disorders, locus-level association profiles across factors, and effect-size distributions. Locus sharing implies overlapping molecular pathways and highlights candidate shared targets for biomarker development.

The high-confidence genetic map supports prioritizing transdiagnostic biomarkers, refining how we communicate polygenic risk across diagnostic categories, and informing trial stratification aligned to biological families.

Key Takeaways:

• Five broad genetic factors explain roughly two-thirds of SNP heritability across 14 psychiatric disorders.
• Shared signals concentrate in excitatory and inhibitory neurons and early developmental windows, supporting transdiagnostic biomarker efforts.
• Hundreds of loci are implicated, with many shared across factors and a smaller subset disorder-specific—suggesting overlapping molecular targets.