Somatic mutations in two genes associated with schizophrenia

Researchers analysed the genomes of more than 20000 blood samples in people with or without schizophrenia, taken from the Psychiatric Genomics Consortium. They found that somatic mutations (non-inherited) in two genes, NRXN1 and ABCB11 correlated with schizophrenia cases when disrupted in utero.
Schizophrenia is a chronic mental disorder characterized by disturbances in thought, perception, emotions, and behaviour, often leading to impaired social functioning.
Schizophrenia is a chronic mental disorder characterized by disturbances in thought, perception, emotions, and behaviour, often leading to impaired social functioning. Now, researchers have associated non-inherited somatic mutations with schizophrenia.


  1. Correlation found between schizophrenia and somatic copy-number variants (CNVs).
  2. Somatic mutations occur in an individual’s body cells after fertilization and are not inherited.
  3. Inherited mutations, present in germ cells, can be passed from parents to offspring.
  4. Copy number variants (CNVs) involve the deletion or duplication of DNA segments, potentially leading to altered gene dosage.
  5. CNVs can be naturally occurring but can also contribute to genetic disorders and diseases.
  6. Researchers identified common somatic CNVs in blood samples of individuals with schizophrenia, suggesting their role in the disorder.
  7. Specific genes (NRXN1 and ABCB11) showed recurring deletions associated with schizophrenia, affecting chromosome connections and response to antipsychotic medication.

In a recent study, researchers found a correlation between schizophrenia and somatic copy-number variants 1. These are a type of mutation that occurs early in development but after genetic material is inherited. The study is one of the first to rigorously describe the relationship between somatic (non-inherited) genetic mutations and schizophrenia risk.

Somatic Mutations

Somatic mutations refer to genetic alterations that occur in the cells of an organism’s body (somatic cells) after fertilisation of the egg and sperm. Therefore, they are not inherited or passed on to future generations.

Somatic mutations affect only the individual in which they occur. These mutations are acquired during a person’s lifetime and are typically not present in the germ cells (sperm and egg) that are responsible for reproduction.

On the other hand, inherited mutations are present in the germ cells and can be passed from parents to their offspring.

Inherited mutations are present in the DNA of every cell in the individual’s body. They can affect the individual’s traits and risk for certain diseases. Inherited mutations can be inherited from one or both parents, and they can be present from the moment of conception. They have the potential to be passed on to future generations.

Copy number variants (CNVs)

Copy number variants (CNVs) are genetic variations that involve the deletion or duplication of relatively large segments of DNA in a person’s genome.

CNVs can result in an abnormal number of copies of a particular gene or genes, leading to altered gene dosage. CNVs can occur naturally and are a normal part of genetic variation in the human population. However, some CNVs are associated with various genetic disorders and can contribute to the development of certain diseases or conditions. In the research study we are discussing today, CNVs in two genes, NRXN1 and ABCB11 were found to be correlating with schizophrenia cases when disrupted in utero

in utero” is a Latin term that translates to “in the womb” and refers to the period of time during which a fetus develops inside the uterus of a pregnant woman. It encompasses the stages of prenatal development from conception to birth, encompassing the growth and maturation of the fetus within the protective environment of the mother’s uterus.


Schizophrenia is a mental disorder that lasts for a long time and is quite complex. It affects how a person thinks, feels, and behaves. People with schizophrenia may experience things that are not real, like hearing or seeing things that others don’t. They may also have trouble organizing their thoughts and speaking clearly. Social withdrawal, difficulty focusing, and emotional ups and downs are common too. Schizophrenia can have a significant impact on a person’s life and their ability to understand and interact with the world around them.

Somatic Mutations and Schizophrenia

The researchers led by Christopher A. Walsh from Boston Children’s Hospital in the USA wanted to understand how certain genetic variations contribute to the risk of schizophrenia. They studied two types of genetic variations: germline copy-number variants (CNVs) that are inherited, and somatic CNVs (sCNVs) that occur in some cells but not all.

To investigate sCNVs, they examined blood samples from 12,834 people with schizophrenia and 11,648 healthy individuals. They focused on sCNVs that appeared frequently in blood disorders, as they could be relevant to schizophrenia.

They found that likely early-developmental sCNVs were more common in people with schizophrenia (0.91%) compared to healthy individuals (0.51%). In five individuals with schizophrenia, they observed recurring deletions in specific parts of the NRXN1 gene, known as exons 1-5.

By examining how chromosomes connect with each other, they also discovered that deletions in NRXN1 gene led to abnormal connections between different regions of the chromosomes. These connections were specific to certain alleles (versions) of the gene.

The researchers also noticed recurring deletions in the ABCB11 gene, which is involved in the response to antipsychotic medication. These deletions were present in five individuals with treatment-resistant schizophrenia. ABCB11 was found to be more prevalent in neurons involved in specific dopamine pathways in the brain.

These findings suggest that sCNVs could play a role in the risk of schizophrenia. The researchers believe that understanding these genetic variations could help us better comprehend the development and treatment of schizophrenia.


  1. Eduardo A. Maury et al., Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions. Cell Genomics. 100356 (2023).
Photo of Sampath Amitash Gadi, author at
Sampath AmitashGadi, Ph.D.
Editor at

Sampath works as a DNA researcher at the University of Copenhagen. Right now, he is studying how proteins and protein signaling help with DNA Damage in cells.

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