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."
To learn more about this study, please visit: Recall-by-genotype of neurodevelopmental disorder copy number variants in a multi-ancestry, healthcare-system biobank | npj Genomic Medicine
