Link between genetics and neuropsychiatric disorders confirmed – Neuroscience News

Summary: 1% of patients enrolled in a health initiative carry at least one rare genetic variant linked to an increased risk of a neuropsychiatric disorder such as schizophrenia or bipolar disorder. A third of people with one variant had been diagnosed with a mental health disorder.

Source: Geisinger Health System

A Geisinger study of more than 90,000 patients found that approximately one in 100 patients carried at least one rare genetic variant known to increase the risk of neuropsychiatric disorders (NPDs), such as schizophrenia and spectrum disorders autism, and that a third of those carrying a variant had a diagnosed mental health problem.

The results, published online by the American Journal of Psychiatryconfirm a strong link between genetics and NPD.

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 the community health initiative MyCode from Geisinger.

The researchers assessed the sequenced exomes for 94 genes that have been linked to an increased risk of NPD and compared the prevalence of these genes with anonymized linked EHR diagnostic codes for NPD, including autism, schizophrenia and the disorder bipolar.

Genetic variants were found in more than 1% of patients in the study group, and one-third of those with a variant had a corresponding diagnosis of NPD.

“This study confirms the important role of rare genetic variants in neuropsychiatric disorders and highlights the use of DNA-based approaches in the study and diagnosis of these conditions,” said Dr. Martin.

“Given that one in 100 MyCode participants were found to have one of these genetic variants, efforts to integrate genetic testing into routine health care have the potential to improve treatment and care. 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 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 NPD, the team wrote. of research.

About this genetics and mental health research news

Author: Press office
Source: Geisinger Health System
Contact: Press office – Geisinger Health System
Image: Image is in public domain

Original research: Access closed.
“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

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Summary

Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population

Objective:

Autism, schizophrenia, and other clinically distinct neurodevelopmental psychiatric disorders (NPDs) have common genetic etiologies, including single-gene and multi-gene copy number (CNV) variants. Because rare variants are primarily studied in clinical cohorts, population-based estimates of their prevalence and penetrance are lacking. The authors determined the prevalence, penetrance, and risk of NPD of pathogenic single gene variants in a large healthcare system population.

Methods :

The authors analyzed linked genomics 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 by exome sequencing, and NPD penetrance was calculated using preselected EHR diagnostic codes. The risk of NPD was estimated using a case-control comparison of DiscovEHR participants with and without a diagnosis of NPD. The results of single gene variant analyzes were also compared with those of 31 previously reported pathogenic NPDs.

Results:

Pathogenic variants were identified in 0.34% of the DiscovEHR cohort and demonstrated 34.3% penetrance for NPDs. Similar to CNVs, sequence variants collectively conferred substantial risk for several NPD diagnoses, including autism, schizophrenia, and bipolar disorder. A significant risk of NPD remained after participants with intellectual disabilities were excluded from the analysis, confirming the association with major psychiatric disorders in people without severe cognitive deficits.

Conclusion :

Collectively, rare single gene variants and CNVs have been found in more than 1% of individuals in a large healthcare system population and play an important contributory role in mental health disorders. Diagnostic genetic testing for pathogenic variants in symptomatic individuals with NPD could improve clinical outcomes through early intervention and anticipatory therapeutic support.