Using Patterns of Genetic Association to Elucidate Shared Genetic Etiologies Across Psychiatric Disorders

Behav Genet. 2017 Jul;47(4):405-415. doi: 10.1007/s10519-017-9844-4. Epub 2017 Mar 25.


Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European-American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance.

Keywords: Comorbidity; GWAS; Genetic etiology; Latent profile analysis; Psychiatric disorder.

MeSH terms

  • Alcoholism / genetics*
  • Antisocial Personality Disorder / genetics*
  • Case-Control Studies
  • Cluster Analysis
  • Comorbidity
  • Depressive Disorder, Major / genetics*
  • Female
  • Genetic Association Studies / methods*
  • Genetic Association Studies / statistics & numerical data
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Male
  • Mental Disorders / genetics
  • Mental Health
  • Polymorphism, Single Nucleotide / genetics
  • Transcriptome / genetics
  • Twins, Dizygotic / genetics
  • Twins, Monozygotic / genetics
  • White People / genetics