Project Details
Description
Abstract
The last decade of clinical progress in intellectual and developmental disabilities (IDD)—which
affect one in six individuals in the U.S.—has been characterized by unprecedented advances in
understanding the nature and complexity of genetic susceptibility to IDD. Rare copy number and
sequence variants are now known to account for a major share of population-attributable risk for
IDD, and are being identified in over 30% of individuals who undergo clinical genomic sequencing.
Clinical identification of pathogenic variants has generated major translational opportunities to
accelerate discovery and improve clinical treatment, but these opportunities are constrained by
serious gaps in our understanding of how to estimate the pathogenicity of a given genetic
abnormality in an individual patient. This U01 Collaborative Innovation Award of the Clinical and
Translational Science Award (CTSA) Program addresses this major roadblock, capitalizing upon
the fact that genomic information is now commonly acquired in clinical settings and substantially
subsidized by U.S. health insurers. Ensuring that clinically-acquired sequencing data of IDD
patients is systematically integrated with standardized information on neurobehavioral variation
and clinical course (this is currently uncommon) stands to accelerate understanding of the
relationship between genetic variation and disease. The aims of this program are to establish
standards for feasible neurobehavioral characterization of IDD patients in clinical health systems
across the CTSA Network, to integrate phenotypic and clinical genomic characterization of
patients to directly promote progress in the national agenda for IDD gene and variant curation,
and to establish a dynamic, state-of-the-art IDD patient registry, as an extension of NCAT’s Center
for Data To Health (CD2H) Initiative. This registry will be designed to co-register phenotypic,
genotypic, and electronic health record data on brain imaging, EEG, laboratory biomarkers, and
clinical course, for the purpose of specifying nuanced profiles of risk, resilience, and intervention
response, and to elucidate both common and rare pathogenic mechanisms in IDD. Once
established, the CTSA-IDD Registry will constitute a self-perpetuating open science platform for
translational advances in IDD, by providing major new opportunity for patients affected by
individually-rare IDD conditions to be identified by qualified scientists and clinicians, to be sub
grouped according to genetic or phenotypic profile, and to participate in focused discovery efforts,
clinical trials, and/or innovations in personalized intervention specific to their conditions.
The last decade of clinical progress in intellectual and developmental disabilities (IDD)—which
affect one in six individuals in the U.S.—has been characterized by unprecedented advances in
understanding the nature and complexity of genetic susceptibility to IDD. Rare copy number and
sequence variants are now known to account for a major share of population-attributable risk for
IDD, and are being identified in over 30% of individuals who undergo clinical genomic sequencing.
Clinical identification of pathogenic variants has generated major translational opportunities to
accelerate discovery and improve clinical treatment, but these opportunities are constrained by
serious gaps in our understanding of how to estimate the pathogenicity of a given genetic
abnormality in an individual patient. This U01 Collaborative Innovation Award of the Clinical and
Translational Science Award (CTSA) Program addresses this major roadblock, capitalizing upon
the fact that genomic information is now commonly acquired in clinical settings and substantially
subsidized by U.S. health insurers. Ensuring that clinically-acquired sequencing data of IDD
patients is systematically integrated with standardized information on neurobehavioral variation
and clinical course (this is currently uncommon) stands to accelerate understanding of the
relationship between genetic variation and disease. The aims of this program are to establish
standards for feasible neurobehavioral characterization of IDD patients in clinical health systems
across the CTSA Network, to integrate phenotypic and clinical genomic characterization of
patients to directly promote progress in the national agenda for IDD gene and variant curation,
and to establish a dynamic, state-of-the-art IDD patient registry, as an extension of NCAT’s Center
for Data To Health (CD2H) Initiative. This registry will be designed to co-register phenotypic,
genotypic, and electronic health record data on brain imaging, EEG, laboratory biomarkers, and
clinical course, for the purpose of specifying nuanced profiles of risk, resilience, and intervention
response, and to elucidate both common and rare pathogenic mechanisms in IDD. Once
established, the CTSA-IDD Registry will constitute a self-perpetuating open science platform for
translational advances in IDD, by providing major new opportunity for patients affected by
individually-rare IDD conditions to be identified by qualified scientists and clinicians, to be sub
grouped according to genetic or phenotypic profile, and to participate in focused discovery efforts,
clinical trials, and/or innovations in personalized intervention specific to their conditions.
Status | Finished |
---|---|
Effective start/end date | 6/5/20 → 30/4/24 |
Links | https://projectreporter.nih.gov/project_info_details.cfm?aid=10629203 |
Funding
- National Center for Advancing Translational Sciences: US$1,236,882.00
- National Center for Advancing Translational Sciences: US$1,252,083.00
- National Center for Advancing Translational Sciences: US$1,193,315.00
ASJC Scopus Subject Areas
- Genetics
- Molecular Biology
- Microbiology
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