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-OD-22-058

Key Dates

Release Date:

January 28, 2022

First Available Due Date:
February 28, 2022
Expiration Date:
March 01, 2022

Related Announcements

NOT-AG-22-017 - Notice of Participation of the National Institute on Aging (NIA) in NOT-OD-22-058, Notice of Special Interest (NOSI): Discovery of the Genetic Basis of Conditions Associated with Down Syndrome for the INCLUDE Project (X01)

PAR-22-054- 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)

NOT-HD-20-039 - 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)

Issued by

Office of The Director, National Institutes of Health (OD)

National Heart, Lung, and Blood Institute (NHLBI)

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

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

Background

Down syndrome is the most common genetic cause of intellectual disability, the most common autosomal trisomy, and one of the most visible and universally recognized genetic syndromes. Each year there are approximately 5300 babies born in the United States with Down syndrome. Within the past 25 years, the average lifespan for a person with Down syndrome has doubled, from 30 to 60 years. Despite this increase in lifespan, individuals with Down syndrome and their families face significant and changing health challenges with age, and they have often been excluded from participation in research that could improve their health outcomes and quality of life. While all people with Down syndrome are connected by the common feature of a complete or partial copy of chromosome 21 (trisomy 21), there are significant physical and cognitive differences among them, indicating that inter-individual variability exists.

Down syndrome is associated with an increased prevalence of autism and epilepsy. About 75% of individuals experience cognitive decline in a syndrome that resembles Alzheimer’s disease but has its onset a decade or two earlier than typical Alzheimer’s disease. Individuals with Down syndrome 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 Down syndrome infrequently develop solid tumors such as breast or prostate cancer, and despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, they rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with Down syndrome, and for individuals who do not have Down syndrome but share these co-occurring conditions.

This FOA is one of several trans-NIH research initiatives created in response to Fiscal Year 2018, 2019, and 2020 Omnibus Appropriations Reports, which encourage NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population, while increasing the pipeline of Down syndrome investigators. Together, the initiatives are called the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Information about projects that were funded in prior years, as well as the NIH INCLUDE Down Syndrome Research Plan, are available on the INCLUDE Project website at https://www.nih.gov/include-project/. The INCLUDE Project has three components:

  • Component 1: Targeted high risk - high reward basic science studies in areas highly relevant to Down syndrome
  • Component 2: Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions
  • Component 3: Inclusive clinical trials of existing and future treatments and interventions for co-occurring conditions in individuals with Down syndrome

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 sequencing, exome sequencing, transcriptome sequencing, and epigenomic assays (e.g., genome-wide methylation profiling, chromatin accessibility assays, ATAC-seq) may be proposed for affected tissue, when justified. This NOSI seeks applications for DNA, RNA, and other 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 the INCLUDE Data Hub in coordination with the INCLUDE Data Coordinating Center (DCC). This NOSI builds off of an existing X01 cohort sequencing opportunity, PAR-22-054. In addition to the childhood cancer and structural birth defects conditions that are a focus of PAR-22-054, 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-22-054- 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-22-054 must be followed, with the following additions:

  • For funding consideration, applicants must include NOT-OD-22-058 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-22-054 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 the appropriateness of the intended resource and research plans for this program, the 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:

Melissa A. Parisi, M.D., Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)
Tel: (301) 435-6880

Email: parisima@mail.nih.gov