Same Genes, Different Disorders

The phenomenon of comorbidity is extremely common in psychiatry.  While the term is used to denote the occurrence of two or more independent psychiatric disorders in the same individual, there is increasing evidence to suggest that different types of psychopathology share common etiologic factors.  This molecular genetic study, recently published in The Lancet, was done to examine the question of whether different categories of disorders were associated with common risk genes.

The study comes from the Psychiatric Genomics Consortium.  It compares a group of 33,332 individuals with various psychiatric disorders to a group of 27,888 controls. The types of psychiatric disorders examined included autistic spectrum dnadisorders, ADHD, bipolar disorder, major depressive disorder, and schizophrenia.  The subjects have previously been involved in genetic studies looking that tried to pair specific genes with a single disorder. The authors performed a genome-wide association study or GWAS that was able to examine associations between these various disorders and single nucleotide polymorphisms or SNPs.

Results showed that four SNPs attained statistical significance at the genome wide level, which controls for the number of tests made. Significant associations were found at four loci, including 3p21, 10q24 and in two SNPs that involved genes that encode for L-type voltage gated calcium channel subunits.  These SNPs were associated with multiple psychiatric disorders, with the two calcium channel signaling genes related to all five disorders tested.

The authors concluded that there was evidence for some common genetic factors that were related to multiple types of disorders.  The authors advocated for a classification system that went beyond symptom description and was informed by disease mechanisms.

This is an important study in many ways.  Clinicians have long been aware of the fact that the boundaries between supposedly distinct categories of disorders are not very clear, and these data suggest that one of the reasons that these lines can be so fuzzy is that many disorders share a common genetic diathesis.  What is significant further is the hint at what exactly these common genes are, giving researchers a potential target for interventions that could cut across many types of psychopathology.


Smoller J et al.  Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. Published online Feb, 2013.

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