Schizophrenia: Rare genetic changes increase risk

• Rare genetic variants that may increase the likelihood of neuropsychiatric disorders (NPDs), such as schizophrenia and bipolar disorder, have been found in around one in 100 people in the general population, according to a new study on over 90,000 individuals.
• The research also revealed that one-third of those with this variant had a diagnosed mental health condition.
• These findings were based on an analysis of genetic and electronic health record (EHR) data focusing on 94 genes linked to increased risk of NPD.

Neurodevelopmental psychiatric disorders (NPDs) are conditions that affect brain development and can cause disabilities. They are very common in the United States, affecting more than 20% of the population.

People with neurodevelopmental disorders can have difficult behaviors and mental health issues. These disorders have complex origins, and are caused by a combination of genetic factors and environmental influences.

Several NPDs, such as schizophrenia, bipolar disorder, and some forms of intellectual disability or developmental delay, have similar genetic causes.

These include different sequences in the DNA on certain parts of the genome, known as variants, which can occur on specific genes that have a big impact on brain function.

Research into these rare genetic variants is important for understanding all NPDs, because it helps reveal shared pathways in the brain that can be disrupted in people with these disorders. This knowledge can lead to new treatments and therapies for people with these conditions.

In this new study, published in the American Journal of Psychiatry, the researchers were able to demonstrate a significant correlation between 94 genetic variants and the risk of developing NPDs.

Their paper lists autism, schizophrenia, and bipolar disorder as NPDs they included in the study.

Genetic data and electronic health records

The research team examined data from a subset of 90,595 participants enrolled in the MyCode Community Health Initiative, the DNA sequencing program at Geisinger, a healthcare delivery and coverage organization.

The study analyzed genetic and electronic health record (EHR) data, focusing on 94 genes that were previously linked to an increased risk of NPDs, including autism, schizophrenia, and bipolar disorder.

They compared the prevalence of these genes with de-identified linked EHR diagnosis codes for NPD.

The study found that more than 1% of participants in the cohort had one of these rare genetic variants linked to NPD, and of those participants, a third had been previously diagnosed with an NPD.

Frequency, impact of rare genetic changes

The research team identified harmful changes in individual genes and their likelihood to cause NPDs in a large healthcare system, which could lead to improved prevention and treatment methods.

They highlight that while hundreds of genes are involved in neuropsychiatric disorders, the study focused on the genes that are currently best understood.

Dr. Christa Lese Martin, chief scientific officer at Geisinger, director of the Autism & Developmental Medicine Institute, and one of the authors of the paper, spoke to Medical News Today, saying that “the study found that approximately one in 100 MyCode participants carry at least one rare gene variant known to increase risk for neuropsychiatric disorders (NPD), such as autism and schizophrenia, and that a third of those with a variant had a diagnosed mental health condition in their medical record.”

Dr. James Giordano, Pellegrino Center professor of neurology and biochemistry at Georgetown University Medical Center, not involved in this research, noted that “this study investigated the frequency of single gene variance of a number of neurodevelopmental psychiatric pathologies, inclusive of autism and schizophrenia spectrum disorders.”

“By examining the genetic profiles of a population-wide sample of symptomatic individuals, the study demonstrated that many present single gene expression that may contribute some predisposition to these conditions,” he commented.

What could these findings mean?

“Even though a significant number of participants with a genetic variant had an existing mental health condition, very few of them were aware of the genetic cause,” said Dr. Lese Martin.

“Our experience is that the majority of participants appreciate learning this information because it helps ‘medicalize’ their condition and removes some of the stigma that is still associated with these conditions,” she noted.

“This study is a first step toward understanding the broad spectrum of mental health conditions observed with specific genetic variants. Moving forward, our research will focus on unique therapies that may benefit people with these specific genetic variants,” Dr. Lese Martin further explained.

Dr. Giordano agreed, saying that “the findings are of interest and potential value in that they demonstrate the relative frequency of single gene expression in these types of disorders within a generalized regional population.”

“However, it is important to note that genetics often only establish a potential for the ultimate development of certain physical and physiological characteristics — which are dependent, at least in part, on a host of environmental factors,” he cautioned.

“Nevertheless, gaining improved understanding of neurogenetics is vital to gaining insights about mechanisms of disease, and possible genetic interventions aimed at mitigating these disorders’ development, expression, and manifestations.”

– Dr. James Giordano

The researchers at Geisinger note that precision medicine has been helpful in making progress in other health conditions like cancer and heart disease, and they believe that it could lead to targeted treatments that work well for NPDs too, however, further research is needed.

Ultimately, this study highlights that testing for these potentially harmful genetic changes among people who have symptoms of NPDs could lead to better outcomes, by allowing for early intervention and specialized treatment.

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