New patterns found in the genetic relationship of 5 major psychiatric disorders
Nature Genetics study co-authored by VCU expert
An international consortium has shown for the first time evidence of substantial overlap of genetic risk factors shared between bipolar disorder, major depressive disorder and schizophrenia and less overlap between those conditions and autism and attention deficit-hyperactivity disorder (ADHD), according to a study published this week in Nature Genetics‘ Advance Online publication.
The root cause of psychiatric illnesses such as bipolar disorder, major depressive disorder schizophrenia, autism and ADHD is not fully understood. For more than 125 years, clinicians have based diagnosis on a collection of symptoms observed in patients.
But, scientists have since identified that the five psychiatric disorders share a common genetic link and are now moving toward understanding the molecular underpinnings of psychiatric illness. The precise degree to which these disorders share common ground has remained unknown, until now.
The project is led by the Cross-Disorder Group of the Psychiatric Genomics Consortium and is the largest genetic study of psychiatric illness to date.
The findings provide insight into the biological pathways that may predispose an individual to disease and could ultimately lead to the development of new therapeutic avenues to treat the five major psychiatric illnesses.
“This is a very large scale study using a new, innovative statistical method,” said study co-senior author Kenneth S. Kendler, M.D., professor of psychiatry, and human and molecular genetics in the Virginia Commonwealth University School of Medicine, and an internationally recognized psychiatric geneticist.
“Prior to this model, we have not been able to address these questions. These results give us by far the clearest picture available to date of the degree of genetic similarity between these key psychiatric disorders. We hope that this will help us both in developing a more scientifically based diagnostic system and understanding the degree of sharing of the biological foundation these illnesses,” he said.
The study builds on findings published earlier this year in The Lancet, which reported that specific single nucleotide polymorphisms, or SNPs, are associated with a range of psychiatric disorders that can occur during childhood or adulthood.
Next, the group will examine other disorders for which molecular genetic data is accumulating including eating disorders, obsessive compulsive disorder and drug use disorders.
Since 2007, the Cross-Disorder Group of the Psychiatric Genomics Consortium has reviewed scientific literature of genome-wide association studies, or GWAS, on psychiatric disorders. To date, GWAS data from more than 19 countries has been gathered by the consortium.
The Nature Genetics study is titled, “Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.”
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear.
To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD).
We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17–29% of the variance in liability.
The genetic correlation calculated using common SNPs was
high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.),
moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.),
bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.),
low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and
non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn’s disease.
This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.