Not just one p - Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities.

  • Type:#blog or#article
  • Year read:#read2021
  • Subject: p-factor GWAS
  • Bibtex: @mallard2019
  • Bibliography: Mallard, T. T., Linnér, R. K., Okbay, A., Grotzinger, A. D., Vlaming, R. de, Meddens, S. F. W., … Harden, K. P. (2019). Not just one p: Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities. BioRxiv, 603134. https://doi.org/10.1101/603134

  • UK Biobank
  • Psychosis, mania and irritability (Schizophrenia, Bipolar disorder, Depression)
  • Genomic SEM to analyse underlying constructs
  • Found two constructs: General vulnerability to self-reported symptoms and transdiagnostic vulnerability to clinically-diagnosed disease. They were modestly correlated (r = .34)

These findings inform criticisms of psychiatric nosology by suggesting that cross-disorder genetic liabilities identified in GWASs of clinician-defined psychiatric disease are relatively distinct from genetic liabilities operating on self-reported symptom variation in the general population.