Overview
- The Nature study pooled GWAS data from 1,056,201 diagnosed individuals and more than five million controls, led by teams at CU Boulder, Harvard, and Mass General Brigham with the Psychiatric Genomics Consortium.
- Statistical modeling grouped the conditions into five genomic factors: compulsive, neurodevelopmental, internalizing, substance use, and a combined schizophrenia–bipolar factor.
- Roughly 70% of schizophrenia’s genetic signal overlaps with bipolar disorder, reflecting high polygenic sharing and few disorder-specific loci.
- Distinct biological patterns emerged, including excitatory-neuron enrichment for the schizophrenia–bipolar factor and oligodendrocyte/glial associations for internalizing disorders, with substance-use signals implicating alcohol-metabolizing enzymes and nicotine receptors.
- The analysis identified 101 genomic regions with correlated effects, including a chromosome 11 hotspot linked to eight disorders, yet interpretation is constrained by European-ancestry bias and pleiotropy with non-psychiatric traits, prompting calls for more diverse and mechanistic studies.