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Large Genomic Study Identifies Five Shared Risk Dimensions Across 14 Psychiatric Disorders

The findings steer research toward biology-first diagnoses, with clinical adoption still premature.

Overview

  • Published in Nature on December 10, the analysis pooled genomes from more than one million people with psychiatric diagnoses plus millions of controls to probe shared inherited risk.
  • Statistical modeling grouped 14 conditions into five genetic factors: schizophrenia–bipolar; internalizing (depression, anxiety, PTSD); neurodevelopmental (ADHD, autism); compulsive (OCD, anorexia, Tourette); and substance-use disorders.
  • Researchers mapped hundreds of shared signals, including 238 genomic regions tied to the cross-disorder factors, with a chromosome 11 hotspot associated with up to eight conditions.
  • Shared variants show brain cell-type patterns, with excitatory-neuron signals prominent for schizophrenia and bipolar disorder and oligodendrocyte signals enriched for internalizing conditions.
  • The results help explain frequent multiple diagnoses, including roughly two-thirds shared risk between schizophrenia and bipolar disorder and about 90% overlap across depression, anxiety and PTSD, though European ancestry bias and limited mechanistic insight preclude near-term clinical use.