Summary: A new study provides a practical framework for recall-by-genotype (RbG) research within large, diverse healthcare system biobanks to advance precision psychiatry.
Researchers utilized Mount Sinai’s BioMe biobank to identify and recontact individuals carrying rare copy number variants (CNVs) linked to high risks of neurodevelopmental disorders, including autism spectrum disorder, intellectual disability, and schizophrenia.
The team successfully recontacted 892 participants across diverse ancestral backgrounds, demonstrating that direct clinical and cognitive phenotyping captures critical diagnostic nuances beyond standard electronic health records (EHRs).
Key Facts
- Targeted Genomic Cohort Recontact: The researchers recontacted 892 BioMe biobank participants, including 335 rare CNV carriers, 217 individuals with schizophrenia without these CNVs, and 340 neurotypical controls.
- Feasibility and Yield Benchmarks: The recruitment effort achieved an 18% response rate, with 8% of total contactees completing in-depth, direct psychiatric and cognitive assessments.
- Diverse Ancestral Representation: Reflecting BioMe’s diverse healthcare population, the finalized evaluation cohort self-identified as 37% African ancestry, 34% Hispanic/Latino ancestry, and 26% European ancestry.
- Deep Phenotyping Superiority: Direct clinical and cognitive evaluations uncovered granular developmental, psychiatric, and cognitive traits that were absent from routine electronic health record (EHR) data.
- Framework for Precision Psychiatry: The operational benchmarks establish a foundation for stratified clinical trials, targeted therapeutic discovery, and improved clinical translation of psychiatric risk variants.
Source: Mount Sinai Hospital
Clinical biobanks that combine genomic data with electronic health records (EHRs) have become powerful resources for discovering genetic variants associated with disease. These biobanks may also be used to identify individuals carrying clinically relevant genetic variants for participation in clinical research focusing on brain health.
A new study published in npj Genomic Medicine demonstrates recall by genotype in a large, diverse healthcare system biobank—providing a practical framework for future precision psychiatry research.
Researchers from the Icahn School of Medicine at Mount Sinai leveraged BioMe, one of the nation’s largest and most diverse healthcare system biobanks, to identify individuals carrying rare copy number variants (CNVs) that substantially increase the risk of neurodevelopmental disorders, including autism spectrum disorder, intellectual disability, and schizophrenia.
The team recontacted 892 BioMe participants—including 335 CNV carriers, 217 individuals with schizophrenia who did not carry these variants, and 340 neurotypical controls—to evaluate whether recall-by-genotype could be successfully implemented.
Overall, 18 percent of participants responded to recruitment and 8 percent completed comprehensive psychiatric and cognitive assessments. The final study cohort reflected the diversity of the BioMe biobank, with participants self-identifying as 37 percent African ancestry, 34 percent Hispanic, and 26 percent European ancestry. Importantly, these detailed evaluations identified developmental, clinical, and cognitive characteristics beyond those captured in routine electronic health records (EHRs), demonstrating the value of direct phenotyping.
The study establishes important operational benchmarks for implementing recall-by-genotype studies within diverse healthcare systems. These findings provide a practical framework for future efforts to identify and characterize individuals carrying clinically relevant genetic variants within healthcare biobanks, particularly for neuropsychiatric disorders. The approach could ultimately improve the clinical translation of psychiatric risk variants and support more personalized strategies for diagnosis, patient stratification, and targeted therapeutics.
“Clinical biobanks with genetic data are an extraordinary resource for genetic discovery, but they also provide unique opportunities for clinical research,” said Rebecca Birnbaum, MD, Assistant Professor of Psychiatry and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and senior author of the paper.
“By recontacting participants carrying rare CNVs for detailed assessments, we demonstrated both opportunities and challenges of the recall-by-genotype study design in a large, diverse healthcare system biobank.”
Key Questions Answered:
A: Recall-by-genotype (RbG) is an approach where researchers search genetic data in biobanks to find individuals with specific genetic variants (such as rare CNVs) and recontact them for detailed clinical evaluations, cognitive tests, or targeted clinical trials.
A: Genomics research has historically overrepresented individuals of European ancestry. The BioMe cohort in this study was 37% African ancestry, 34% Hispanic, and 26% European ancestry, ensuring that recall-by-genotype benchmarks and psychiatric risk discoveries apply across diverse populations.
A: While electronic health records (EHRs) offer valuable high-level medical histories, direct psychiatric and cognitive assessments revealed specific developmental, cognitive, and clinical nuances essential for precision diagnosis and patient stratification that routine EHR billing codes miss.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and mental health research news
Author: Elizabeth Dowling
Source: Mount Sinai Hospital
Contact: Elizabeth Dowling – Mount Sinai Hospital
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Recall-by-genotype of neurodevelopmental disorder copy number variants in a multi-ancestry, healthcare-system biobank” by Nina Zaks, Behrang Mahjani, Abraham Reichenberg & Rebecca Birnbaum. npj Genomic Medicine
DOI:10.1038/s41525-026-00597-6
Abstract
Recall-by-genotype of neurodevelopmental disorder copy number variants in a multi-ancestry, healthcare-system biobank
Clinical biobanks linking electronic health records (EHRs) with genotype data enable the study of genomic risk factors in real-world populations. However, recall-by-genotype (RbG) of psychiatric risk variants in diverse healthcare-system biobanks remains scarce.
Leveraging BioMe, a multi-ancestry biobank within the Mount Sinai Health System, we recalled carriers of rare copy number variants (CNVs) that confer increased risk for neurodevelopmental disorders (NDDs) to establish empirical benchmarks for RbG implementation.
We recontacted 892 participants: 335 NDD CNV carriers, 217 individuals with schizophrenia without NDD CNVs, and 340 neurotypical controls without NDD CNVs. Participants completed clinical and cognitive assessments. Overall, 18% of recontacted participants responded to recruitment, and 8% completed the study: 30 NDD CNV carriers, 20 individuals with schizophrenia, and 23 controls.
The mean age was 48.8 years, 66% were female, and self-reported ancestry was 37% African, 34% Hispanic, and 26% European. Seventy percent of NDD CNV carriers had at least one neuropsychiatric or developmental condition, including mood or anxiety disorders (40%). Among 22 NDD CNV carriers at loci implicated in impaired cognition, performance was lower than controls on Digit Span Backward (β = –1.76, FDR = 0.04) and Digit Span Sequencing (β = −2.01, FDR = 0.04). NDD CNV carriers also outperformed the schizophrenia group on verbal learning (β = 4.5, FDR = 0.05).
Recall of individuals—including those with psychiatric illness—yielded phenotypes not captured in EHRs and provides empirical benchmarks relevant to RbG implementation and precision psychiatry in diverse healthcare systems.
