The National Institutes of Health INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project: Accelerating research discoveries for people with Down syndrome across the lifespan.

The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de-identified clinical information and multi-omics data from research participants for broad data sharing and secondary analyses. Through the DS-Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan.

Trends in National Institutes of Health-Funded Congenital Heart Disease Research from 2005 to 2015.

In an era of ongoing need for research to enable evidence-based care for the expanding population with congenital heart disease (CHD), economic fluctuations have impacted research funding. We characterize trends in NIH-funded CHD research from 2005 to 2015. We searched the NIH RePORTER database from 2005 to 2015 using the terms "congenital heart" and "cardiac morphogenesis". Projects were characterized by year, institute, mechanism, costs, type and topic, and funding trends were analyzed. From 2005 to 2015, NIH funded 633 CHD research projects with total costs of $991 million. The National Heart, Lung, and Blood Institute funded 83% of CHD projects (528, $857 million). The R01 mechanism was used for 45% of projects (288, $421 million). Projects were 70% basic/early translational research, 27% clinical research, and 3% both. Cardiac developmental biology was the most common topic (52%), followed by technology/therapy development (15%), and diagnosis/management (12%). The total number of CHD projects ranged from 153 to 221 per year (30-58 new projects/year), and costs per year ranged from $58 to $116 million. The number of projects and total costs increased until 2012, but decreased again thereafter. CHD research did not experience as much erosion as overall NIH purchasing power; in constant dollars, CHD research funding levels in 2015 were $12 million higher than those in 2005. The NIH supported a diverse portfolio of CHD projects from 2005 to 2015. Support of CHD research projects trended upward until 2012, but declined thereafter due to fiscal austerity measures.

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.