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 and 2019, 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

This Notice of Special Interest (NOSI) announces NIH support for the professional development of trainees aiming to establish a career in DS-related research. By providing these scientists with training, resources, and mentorship, the NIH intends to foster a pipeline of investigators in DS and other intellectual disabilities who will lead future research to improve the understanding of the biology of DS and support development of new treatments for health conditions experienced by those with DS. Investigators early in their careers (e.g., predoctoral candidates) as well as those with advanced degrees (e.g., PhD, MD) may benefit from mentorship from established investigators and professionals in the DS research community in basic science fields as well as clinical and translational arenas.

The NIH is issuing this NOSI to expand the community of investigators conducting research related to DS by encouraging scientists and physicians early in their research careers to develop research projects related to co-occurring conditions associated with DS. Sharing of resources and effective communication of outputs to the broader communities are a high priority of the INCLUDE Project. Applicants responding to this NOSI are strongly encouraged to describe plans for rapid sharing of data and results as well as innovative data analytics approaches (see Goal 3, NIH Strategic Plan For Data Science).

A list of Funding Priorities by Institute and Center for the project is available on the INCLUDE website. Applications in response to this NOSI should be aligned with the overall INCLUDE Project Research Plan, which consists of three components:

• Component 1: Targeted, high risk-high reward, basic science studies in areas highly relevant to Down syndrome
• Component 2: Cohort Study to connect existing resources and expand to inclusion of individuals with Down syndrome
• Component 3: Inclusive clinical trials research for co-occurring conditions in individuals with Down syndrome

Projects that propose to recruit subjects with DS are encouraged to promote enrollment of research subjects in the DS patient registry supported by NIH, DS-Connect . For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use biorepositories designated by INCLUDE staff that meet requirements for broad sharing. An NIH resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing.

Application and Submission Information

This Notice applies to due dates on or after April 8, 2020 and expires on January 8, 2022.

Applications in response to this NOSI must be submitted using one of the following target funding opportunity Announcements (FOAs) or their reissued equivalents. Although not all NIH components indicated above are listed as Participating Organizations in all FOAs listed below, applications for this special topic will be accepted.

• PA-19-191 Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions with NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30)
• PA-19-192 Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions Without NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30)
• PA-19-195 Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31)
• PA-19-196 Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31 - Diversity)
• PA-19-188 Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (Parent F32)

All instructions in the SF424 (R&R) Application Guide and the listed funding opportunity announcements must be followed, with the following addition:

• For funding consideration, applicants must include NOT-OD-20-020 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.

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

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

A list of contacts for each participating NIH Institute and Center is available on the INCLUDE website.