From the Guidelines
Schizophrenia has a strong genetic component, with heritability estimated at 80%, as evidenced by a recent study 1, indicating that genetics play a crucial role in the risk of developing the disorder. The genetic basis of schizophrenia is complex and involves multiple genes with small effects, as well as rare variants with larger effects.
- Notable risk genes include those that affect neurodevelopment, synaptic function, and dopamine regulation, such as DISC1, COMT, NRG1, and DTNBP1.
- Copy number variations (CNVs), particularly deletions in chromosomal regions 22q11.2, 1q21.1, and 15q13.3, significantly increase schizophrenia risk.
- Environmental factors, such as prenatal infections, birth complications, childhood trauma, and cannabis use, interact with genetic predisposition and can potentially trigger the disorder in genetically vulnerable individuals. The genetic architecture of schizophrenia involves thousands of common genetic variants, each with small effects, and rare variants with larger effects, making it a complex polygenic disorder.
- First-degree relatives of individuals with schizophrenia have approximately a 10% risk of developing the condition, compared to the general population risk of about 1% 1.
- While genetic testing is not currently used for clinical diagnosis, understanding the genetic basis of schizophrenia helps explain familial patterns and may eventually lead to personalized treatment approaches targeting specific biological pathways affected by an individual's genetic profile. It is essential to consider the genetic basis of schizophrenia in the context of its complex interplay with environmental factors, as this understanding can inform treatment strategies and improve patient outcomes.
- A recent study 1 highlights the importance of considering the genetic basis of schizophrenia in the development of personalized treatment approaches.
- Another study 1 emphasizes the need for early intervention and treatment to prevent long-term morbidity and improve cognitive function in individuals with schizophrenia.
From the Research
Genetic Basis of Schizophrenia
The genetic basis of schizophrenia is complex and involves the interaction of multiple genetic and environmental factors.
- Schizophrenia is a polygenic disorder, meaning that it is caused by the combined action of multiple genes, rather than a single gene 2.
- Genome-wide association studies (GWAS) have been used to identify novel risk genetic factors for schizophrenia, and several susceptibility genes have been identified, including NRG1, DISC1, RELN, BDNF, and MSI2 2.
- The interaction between genetic and environmental factors is also important in the development of schizophrenia, with certain environmental exposures only being of consequence given a specific genetic makeup 3, 4.
Genetic and Environmental Interactions
The interaction between genetic and environmental factors is crucial to understanding the pathogenesis of schizophrenia.
- Environmental factors such as obstetric complications, infections, winter or spring birth, migration, urban living, childhood adversity, and cannabis use have been associated with an increased risk of developing schizophrenia 4.
- Gene-environment interaction studies have shown that certain genetic variants can moderate the effect of environmental exposures on the risk of developing psychosis 3.
- The identification of genetic and environmental interactions is important for developing individualized treatments and prevention plans for schizophrenia 3, 4.
Current Understanding and Future Directions
The current understanding of the genetic basis of schizophrenia is based on a large body of research, including genetic association studies and GWAS.
- Further research is needed to fully understand the genetic and environmental factors that contribute to the development of schizophrenia, and to identify new therapeutic targets for the treatment of the disorder 2, 5, 6.
- The use of polygenic risk scores and genome-wide data offers enhanced prospects for revealing genetic interactions with environmental exposures that contribute to the risk of schizophrenia 4.