Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder

Thomas G. Schulze, Nirmala Akula, René Breuer, Jo Steele, Michael A. Nalls, Andrew B. Singleton, Franziska A. Degenhardt, Markus M. Nöthen, Sven Cichon, Marcella Rietschel, Francis J. McMahon

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Objectives. Genome-wide association studies (GWAS) in complex phenotypes, including psychiatric disorders, have yielded many replicated findings, yet individual markers account for only a small fraction of the inherited differences in risk. We tested the performance of polygenic models in discriminating between cases and healthy controls and among cases with distinct psychiatric diagnoses. Methods. GWAS results in bipolar disorder (BD), major depressive disorder (MDD), schizophrenia (SZ), and Parkinson's disease (PD) were used to assign weights to individual alleles, based on odds ratios. These weights were used to calculate allele scores for individual cases and controls in independent samples, summing across many single nucleotide polymorphisms (SNPs). How well allele scores discriminated between cases and controls and between cases with different disorders was tested by logistic regression. Results. Large sets of SNPs were needed to achieve even modest discrimination between cases and controls. The most informative SNPs were overlapping in BD, SZ, and MDD, with correlated effect sizes. Little or no overlap was seen between allele scores for psychiatric disorders and those for PD. Conclusions. BD, SZ, and MDD all share a similar polygenic component, but the polygenic models tested lack discriminative accuracy and are unlikely to be useful for clinical diagnosis.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalWorld Journal of Biological Psychiatry
Issue number3
StatePublished - Apr 2014
Externally publishedYes


  • Allele burden
  • Genome-wide association
  • Polygenic model
  • Prediction
  • Psychosis

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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