title: Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Göttingen , Göttingen , Germany.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Nirmala
authors.initials: N
authors.lastname: Akula
authors.forename: René
authors.initials: R
authors.lastname: Breuer
authors.forename: Jo
authors.initials: J
authors.lastname: Steele
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalls
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Franziska A
authors.initials: FA
authors.lastname: Degenhardt
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D008297:Male; D008957:Models, Genetic; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*