Summary: 1% of patients registered in a health initiative carry at least one rare gene variant linked to an increased risk of a neuropsychiatric disorder such as schizophrenia or bipolar disorder. One-third of those with a variant had been diagnosed with a mental health disorder.
Source: Geisinger Health System
A Geisinger study of more than 90,000 patients revealed that approximately one in 100 carried at least one rare gene variant known to increase risk for 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 Psychiatry, confirm a strong link between genetics and NPD.
The Geisinger 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.
Researchers evaluated the sequenced exomes for 94 genes that have been linked to an increased risk for NPD and compared the prevalence of these genes with de-identified linked EHR diagnosis codes for NPD, including autism, schizophrenia and bipolar disorder.
Genetic variants were found in more than 1% of patients in the study group, and a 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 in studying and diagnosing these conditions,” Dr. Martin said.
“Given that one in 100 MyCode participants were found to have one of these genetic variants, efforts to incorporate genetic screening into routine healthcare have the potential to improve the treatment and care of individuals 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., a lead author of the study.
Similar precision medicine strategies have accelerated breakthroughs in other health conditions, such as cancer and cardiovascular disease, and have the potential to lead to the discovery of effective targeted treatments for NPDs, the research team wrote.
About this genetics and mental health research news
Original Research: Closed access.
“Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population” by Hermela Shimelis et al. American Journal of Psychiatry
Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population
Autism, schizophrenia, and other clinically distinct neurodevelopmental psychiatric 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 NPD risk of pathogenic single-gene variants in a large health care system population.
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. Loss-of-function pathogenic variants in 94 high-confidence NPD genes were identified through exome sequencing, and NPD penetrance was calculated using preselected EHR diagnosis codes. NPD risk was estimated using a case-control comparison of DiscovEHR participants with and without NPD diagnoses. Results from single-gene variant analyses were also compared with those from 31 previously reported pathogenic NPD CNVs.
Pathogenic variants were identified in 0.34% of the DiscovEHR cohort and demonstrated a 34.3% penetrance for NPDs. Similar to CNVs, sequence variants collectively conferred a substantial risk for several NPD diagnoses, including autism, schizophrenia, and bipolar disorder. Significant NPD risk remained after participants with intellectual disability were excluded from the analysis, confirming the association with major psychiatric disorders in individuals without severe cognitive deficits.
Collectively, rare single-gene variants and CNVs were found in >1% of individuals in a large health care system population and play an important contributory role in mental health disorders. Diagnostic genetic testing for pathogenic variants among symptomatic individuals with NPDs could improve clinical outcomes through early intervention and anticipatory therapeutic support.