The NeuroBioBank whole-genome catalogue of human brain donors with central nervous system disorders

CNS diseases are a prevailing cause of morbidity and mortality worldwide, and are influenced by environmental and biological factors, including genetic risk. Here, we generated genome-wide genetic data on a large cohort of brain tissue donors with in-depth clinical and neuropathological phenotyping, allowing for broad investigations into the risk and mechanisms of these neurological, neurodevelopmental, and psychiatric conditions. This resource consists of 9,663 donors with array-based genotyping and 9,543 donors with whole-genome sequencing completed. The clinical diagnoses of these donors include 148 central nervous system diseases clustered into 15 broad categories by International Classification of Diseases-10 (ICD-10) coding. These donors were collected by six repositories comprising the National Institutes of Health NeuroBioBank, with an average participant age of 60 years. While primarily older individuals of European descent, the cohort also contains younger donors and individuals from non-European backgrounds. Variants were detected in whole-genome sequencing (WGS), normalized and annotated to describe their functional impact, resulting in 171,121,209 unique variants and 1,078,774 non-silent variants. These raw and normalized data have been made available as a neurogenomics resource in the National Institute of Mental Health Data Archive (NIMH NDA) (nda.nih.gov), combined with donor-matched deep demographic and phenotypic data from the NeuroBioBank Portal (neurobiobank.nih.gov). To illustrate applications, we replicated the strong association observed in previous studies between pathogenic CAG nucleotide repeat expansions in the HTT gene with the clinical diagnosis of Huntington's disease, as well as associations of the APOE gene with Alzheimer's disease, and examined the association of polygenic risk scores with the three most common disease diagnoses in the cohort.

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Publication Details

Journal
Brain
Published
2026-02-13
DOI
https://doi.org/10.1093/brain/awag057
Primary Topic
Genetic Neurodegenerative Diseases
Type
article
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article

The NeuroBioBank whole-genome catalogue of human brain donors with central nervous system disorders

Tina Zheng, C. Alba, R. Paul Johnson, David J. Ennulat et al.
Brain
Genetic Neurodegenerative Diseases
article

The NeuroBioBank whole-genome catalogue of human brain donors with central nervous system disorders

Tina Zheng, C. Alba, R. Paul Johnson, David J. Ennulat, John Rosenberger, Patrice L. Whitehead, Torsten Klengel, Eric Dun Ho, Michael Chatigny, D. P. Purohit, Grace Smith, Tori Turpin, Gabriela Höher, John M. Esposito, Rashed M. Nagra, Alexandra LeFevre, Thomas G. Blanchard, José Ramón Fernández Lorenzo, Aya Zeabi, Elizabeth Rice, Kathleen M. Sullivan, Regina Vontell, Derek H. Oakley, Sabina Berretta, William Scott, Susanna P. Garamszegi, Neda R. Morakabati, Julianna K. Martin, Kiely Morris, Darren Chernicky, Isabelle G. Darling, Phyllis Oduor, Lorelle A. Sang, Catalina J. Tabit, Griffin S. Parker, Amanda R. Sandford, Michael Wysocki, Myrtha M. Constant, C. L. Marino, Elisabeth Lawton, Allison P. Rodgers, Maxwell Bustamante, Jill Glausier, Daniel Hupalo, Ioanna Konidari, Matthew D. Wilkerson, Gauthaman Sukumar, Vahram Haroutunian, Miranda Tompkins, Lissette Gomez, Anthony J Griswold, Jacob L McCauley, W Brad Ruzicka, Xiaoyan Sun, David A Davis, David A Lewis, Julianna Pascual, S Humayun Gultekin, Clifton L Dalgard
article en

Abstract

CNS diseases are a prevailing cause of morbidity and mortality worldwide, and are influenced by environmental and biological factors, including genetic risk. Here, we generated genome-wide genetic data on a large cohort of brain tissue donors with in-depth clinical and neuropathological phenotyping, allowing for broad investigations into the risk and mechanisms of these neurological, neurodevelopmental, and psychiatric conditions. This resource consists of 9,663 donors with array-based genotyping and 9,543 donors with whole-genome sequencing completed. The clinical diagnoses of these donors include 148 central nervous system diseases clustered into 15 broad categories by International Classification of Diseases-10 (ICD-10) coding. These donors were collected by six repositories comprising the National Institutes of Health NeuroBioBank, with an average participant age of 60 years. While primarily older individuals of European descent, the cohort also contains younger donors and individuals from non-European backgrounds. Variants were detected in whole-genome sequencing (WGS), normalized and annotated to describe their functional impact, resulting in 171,121,209 unique variants and 1,078,774 non-silent variants. These raw and normalized data have been made available as a neurogenomics resource in the National Institute of Mental Health Data Archive (NIMH NDA) (nda.nih.gov), combined with donor-matched deep demographic and phenotypic data from the NeuroBioBank Portal (neurobiobank.nih.gov). To illustrate applications, we replicated the strong association observed in previous studies between pathogenic CAG nucleotide repeat expansions in the HTT gene with the clinical diagnosis of Huntington's disease, as well as associations of the APOE gene with Alzheimer's disease, and examined the association of polygenic risk scores with the three most common disease diagnoses in the cohort.

Brain
Broad Institute (US), University of Maryland, Baltimore (US), Henry M. Jackson Foundation (US), Allen Institute for Brain Science (US), University of Maryland Medical Center (US), Harvard University (US), University of Miami (US), Uniformed Services University of the Health Sciences (US), University of Pittsburgh (US), McLean Hospital (US), James J. Peters VA Medical Center (US), Brentwood Biomedical Research Institute (US), Icahn School of Medicine at Mount Sinai (US)
Openalex Percentile: Top 56%
Genetic Neurodegenerative Diseases
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