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 journalArticle

Abstract

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
Volume15
Issue number3
DOIs
StatePublished - Apr 2014
Externally publishedYes

Fingerprint

Major Depressive Disorder
Bipolar Disorder
Molecular Biology
Schizophrenia
Alleles
Single Nucleotide Polymorphism
Genome-Wide Association Study
Parkinson Disease
Psychiatry
Weights and Measures
Mental Disorders
Logistic Models
Odds Ratio
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry
  • Psychiatry and Mental health

Cite this

Schulze, T. G., Akula, N., Breuer, R., Steele, J., Nalls, M. A., Singleton, A. B., ... McMahon, F. J. (2014). Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder. World Journal of Biological Psychiatry, 15(3), 200-208. https://doi.org/10.3109/15622975.2012.662282

Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder. / Schulze, Thomas G.; Akula, Nirmala; Breuer, René; Steele, Jo; Nalls, Michael A.; Singleton, Andrew B.; Degenhardt, Franziska A.; Nöthen, Markus M.; Cichon, Sven; Rietschel, Marcella; McMahon, Francis J.

In: World Journal of Biological Psychiatry, Vol. 15, No. 3, 04.2014, p. 200-208.

Research output: Contribution to journalArticle

Schulze, TG, Akula, N, Breuer, R, Steele, J, Nalls, MA, Singleton, AB, Degenhardt, FA, Nöthen, MM, Cichon, S, Rietschel, M & McMahon, FJ 2014, 'Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder', World Journal of Biological Psychiatry, vol. 15, no. 3, pp. 200-208. https://doi.org/10.3109/15622975.2012.662282
Schulze, Thomas G. ; Akula, Nirmala ; Breuer, René ; Steele, Jo ; Nalls, Michael A. ; Singleton, Andrew B. ; Degenhardt, Franziska A. ; Nöthen, Markus M. ; Cichon, Sven ; Rietschel, Marcella ; McMahon, Francis J. / Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder. In: World Journal of Biological Psychiatry. 2014 ; Vol. 15, No. 3. pp. 200-208.
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