Summary

This large genetic case-control study of schizophrenia identified 108 distinct loci associated with schizophrenia, including many novel findings, which have the potential to better understand schizophrenia and may lead to new treatments. Findings were also consistent with known pathophysiology, including involvement of dopamine receptor D2 (the target of antipsychotics), glutamatergic neurotransmission, and voltage-gated calcium channels, as well as genes associated with immunity.

Design

• N=36,989 cases (schizophrenia).
• N=113,075 controls.
• Multi-stage genome-wide association study (GWAS).
• 9.5 million variants considered.

Results

• 128 independent associations identified, enriched among genes expressed in the brain, and genes related to immunity. Associated loci separated by less than 250 kb were merged, resulting in 108 distinct associated loci, 83 of which have not been previously associated with schizophrenia.
• Associations notable for their role in pathophysiology:
  • DRD2, the target of antipsychotic medications.
  • Genes associated with glutamatergic neurotransmission.
  • Genes encoding subunits of voltage-gated calcium channels (previously implicated in schizophrenia).

Reference

Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421-427. doi:10.1038/nature13595.