Notice of Special Interest (NOSI): Discovery of the Genetic Basis of Conditions Associated with Down Syndrome for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project (X01)
Notice Number:
NOT-HD-20-039

Key Dates

Release Date:

December 16, 2020

First Available Due Date:
February 19, 2021
Expiration Date:
February 20, 2021

Related Announcements

PAR-21-040 - Discovery of the Genetic Basis of Childhood Cancers and of Structural Birth Defects: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed)

Issued by

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Purpose

Background

The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018 and 2019 Omnibus Appropriations Reports, which encouraged the NIH to expand its current efforts on Down syndrome (DS) and common co-occurring conditions also seen in the general population while increasing the pipeline of DS investigators. Information about projects that were funded in 2018-2020, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

Individuals with DS face significant and changing health challenges but have often been excluded from participation in research that could improve their health outcomes and quality of life. This population is understudied even though DS is the most common genetic cause of intellectual and developmental disabilities (IDD) and, in the past 25 years, the average lifespan has doubled from 30 to 60 years. In addition to intellectual disability, DS is associated with an increased prevalence of autism and epilepsy. About 75% of individuals with DS experience cognitive decline in a syndrome that resembles Alzheimer’s disease, but with onset a decade or two earlier than typical Alzheimer’s disease. Individuals with DS also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with DS infrequently develop solid tumors such as breast or prostate cancer. Despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, people with DS rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with DS and for individuals who do not have DS but who share these co-occurring conditions.

Research Objectives

The purpose of this Notice of Special Interest (NOSI) is to support the whole genome sequencing of cohort projects that seek to elucidate the genetic etiology of conditions that co-occur with Down syndrome and that meet programmatic objectives for the INCLUDE Project. In addition to whole genome sequencing of germline or constitutional DNA, whole genome, exome, and transcriptome sequencing may be proposed for affected tissue, when justified. This NOSI seeks applications for DNA and RNA sample sets that can be ready for sequencing, as soon as possible after the application due date of this FOA. All sequence data and associated clinical and phenotypic data will be deposited to a NIH designated data repository, such as dbGaP, in coordination with the INCLUDE Data Coordinating Center (DCC).This NOSI builds off of an existing X01 cohort sequencing opportunity, PAR-21-040. In addition to the childhood cancer and structural birth defects conditions that are a focus of PAR-21-040, INCLUDE X01 sequencing proposals can address one or more of the Funding Priorities by Institute and Center described on the INCLUDE website, which also contains a list of contacts for each participating NIH Institute and Center. Applications in response to this NOSI should be aligned with the overall INCLUDE Project Research Plan. Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect®.

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent:

  • PAR-21-040 - Discovery of the Genetic Basis of Childhood Cancers and of Structural Birth Defects: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and PAR-21-040 must be followed, with the following additions:

  • For funding consideration, applicants must include NOT-HD-20-039 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
  • The Research Strategy section of INCLUDE applications should follow instructions contained in PAR-21-040 in the subsection entitled, “For cohorts with structural birth defects”. Responses to the individual instructions in that section should be related to Down syndrome and its co-occurring conditions.

Program Directors/Principal Investigators (PD/PIs) planning to submit applications in response to this NOSI are strongly encouraged to contact the scientific contacts of this NOSI prior to submission to be advised on appropriateness of the intended resource and research plans for this program, competitiveness of a potential application, and alignment with program priorities of the INCLUDE initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Valerie Cotton
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-1519
Email: valerie.cotton@nih.gov


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