Summary: 1% of patients enrolled in a health initiative carry at least one rare genetic variant linked to increased risk of a neuropsychiatric disorder such as schizophrenia or bipolar disorder. A third of those with a variant had been diagnosed with a mental health disorder.
Font: Geisinger Health System
A Geisinger study of more than 90,000 patients revealed that about one in 100 carried at least one rare genetic variant known to increase the risk of neuropsychiatric disorders (NPD), such as schizophrenia and autism spectrum disorder, and that a third of those with a variant had a diagnosed mental health condition.
The results, published online by the american journal of psychiatryconfirm a strong link between genetics and HPN.
Geisinger’s team, led by Christa L. Martin, Ph.D., analyzed genetic and electronic health record (EHR) data from a subset of 90,595 participants enrolled in Geisinger’s MyCode Community Health Initiative.
The researchers evaluated the sequenced exomes of 94 genes that have been linked to increased risk of NPD and compared the prevalence of these genes with unidentified linked EHR diagnostic codes for NPD, including autism, schizophrenia, and bipolar disorder.
Genetic variants were found in more than 1% of patients in the study group, and one-third of those with a variant had been diagnosed with a corresponding NPD.
“This study confirms the important role of rare genetic variants in neuropsychiatric disorders and highlights the use of DNA-based approaches to study and diagnose these conditions,” Dr. Martin said.
“Given that one in 100 MyCode participants was found to have one of these gene variants, efforts to incorporate genetic screening into routine medical care have the potential to improve the treatment and care of people with neuropsychiatric disorders.” .
“We know that hundreds of genes contribute to neuropsychiatric disorders; however, for this study, we focused on those that are currently best understood,” said Hermela Shimelis, Ph.D., lead author of the study.
Similar precision medicine strategies have accelerated advances in other health conditions, such as cancer and cardiovascular disease, and have the potential to lead to the discovery of effective targeted treatments for HPN, the research team wrote.
About this research news in genetics and mental health
original research: closed access.
“Prevalence and penetration of rare pathogenic variants in psychiatric neurodevelopmental genes in a population of the health care system” by Hermela Shimelis et al. american journal of psychiatry
Prevalence and penetration of rare pathogenic variants in psychiatric neurodevelopmental genes in a population of the health care system
Autism, schizophrenia, and other clinically distinct psychiatric neurodevelopmental disorders (NPDs) have shared genetic etiologies, including single-gene and multigenic copy number variants (CNVs). Because rare variants are primarily investigated in clinical cohorts, population-based estimates of their prevalence and penetrance are lacking. The authors determined the prevalence, penetrance, and risk of HPN of single-gene pathogenic variants in a large population of the health care system.
The authors analyzed linked genomic and electronic health record (EHR) data in a subset of 90,595 participants from Geisinger’s MyCode Community Health Initiative, known as the DiscovEHR cohort. Pathogenic loss-of-function variants in 94 high-confidence NPD genes were identified through exome sequencing, and NPD penetrance was calculated using preselected EHR diagnostic codes. The risk of HPN was calculated using a case-control comparison of DiscovEHR participants with and without HPN diagnoses. Results from single gene variant analyzes were also compared with those of 31 previously reported pathogenic NPD CNVs.
Pathogenic variants were identified in 0.34% of the DiscovEHR cohort and demonstrated a penetrance of 34.3% for NPDs. Similar to CNVs, the sequence variants collectively conferred substantial risk for several NPD diagnoses, including autism, schizophrenia, and bipolar disorder. A significant risk of HPN remained after participants with intellectual disabilities were excluded from the analysis, confirming the association with major psychiatric disorders in individuals without severe cognitive deficits.
Collectively, rare single gene and CNV variants have been found in > 1% of individuals in a large population in the health care system and play an important role in mental health disorders. Diagnostic genetic testing for pathogenic variants among symptomatic individuals with HPN could improve clinical outcomes through early intervention and proactive therapeutic support.