A recent study published in the American Journal of Psychiatry has provided new insights into the genetic basis of mental disorders. The authors found that genetic variants associated with a particular mental disorder are highly likely to affect our risk of acquiring another mental disorder. Interestingly, these genetic variants also affect human traits such as intelligence and personality. This indicates that the majority of "genes for depression" are also "genes for intelligence" and "genes for personality". The findings of genetic overlap have important implications for how we interpret genetic discoveries, define mental disorders, and design future genetic prediction tools for mental disorders which may help to improve their management and prevention.
Genetic differences between individuals provide the biological foundations from which mental disorders develop. However, mental disorders are not caused by one single gene. Instead, it is now understood that disorders such as depression and schizophrenia are driven by thousands of genetic variants in a complex interplay with environmental factors. However, despite extensive research over the last 20 years, just a small fraction of the genetic components of mental disorders have so far been discovered.
Studied the genetic variants of more than 200,000 individuals with mental disorders
The current study included genetic data from more than 200,000 individuals with mental disorders. Using novel and advanced statistical tools, the researchers predicted the number of genetic variants shared across depression, bipolar disorder, schizophrenia, and ADHD, as well as measures of cognition and personality.
The findings provide an important conceptual shift
The analyses revealed that many genetic variants were overlapping across disorders. This implies that genetic variants that affect the risk of acquiring a mental disorder are highly likely to affect the risk of acquiring another disorder as well. Surprisingly, there was also a similar pattern of extensive genetic overlap with cognition and personality, indicating that most genetic variants related to mental disorders were also associated with variants for intelligence and personality traits such as neuroticism.
Given the extent of genetic overlap observed, these findings provide an important conceptual shift in how we think about the genetic foundations of mental disorders. Instead of a small number of genes specifically affecting our chances of developing schizophrenia, we show that there are most likely thousands of genetic variants that matter, and these are also likely to affect other human traits such as personality and cognition".
Guy Hindley, Lead Author
We may need to change the definition of mental disorders
Since the current study only estimates the number of genetic variants linked to each mental disorder, future work is required to identify the genes themselves. Nevertheless, these findings indicate that changes in the way in which we define mental disorders may be required to enable better differentiation of the biological mechanisms underlying their genetic risk and to improve genetic prediction. This is important because improved genetic prediction may enable the identification of individuals at risk of mental disorders before disease onset, which may help preventative strategies. Better genetic prediction may also allow treatment to be tailored to the individual, instead of the "one-size fits all" approach which is currently the status quo for most mental disorders.
The "Cross-Trait MiXeR" study is a collaboration between the Norwegian Centre for Mental Disorders Research (NORMENT) at the University of Oslo and Oslo University Hospital and the Department of Radiology at the University of California: San Diego. The authors emphasize the importance of data sharing and large-scale international collaborations as part of this global effort.
Hindley, G., et al. (2022) Charting the Landscape of Genetic Overlap Between Mental Disorders and Related Traits Beyond Genetic Correlation. American Journal of Psychiatry. doi.org/10.1176/appi.ajp.21101051.