Researchers from the University of Colorado Anschutz Linda Crnic Institute for Down Syndrome announced on July 23 the discovery of unique biological processes among individuals with Down syndrome who have different sets of co-occurring conditions. The findings, published in Nature Communications, represent a step toward more personalized treatment approaches for people with Down syndrome.
The study is part of the Human Trisome Project, which is one of the largest and most comprehensive studies focusing on individuals with Down syndrome. The project includes extensive clinical data, multi-omics datasets, and what researchers describe as the largest biobank for studying this condition to date. By analyzing hundreds of blood samples, the research team identified physiological differences across participants who have histories of medical conditions that are more common in this population. They mapped changes in gene expression, protein levels, metabolite abundance, and immune cell types across 100 different clinical traits.
"These results decipher for the first time the conserved effects of the extra copy of chromosome 21 versus effects that are unique or exacerbated in people with Down syndrome that have other co-occurring medical conditions," said Joaquín Espinosa, PhD, executive director of the Crnic Institute and senior author. "We know that no two individuals with Down syndrome are the same from a clinical standpoint, and now we can understand how this uniqueness reflects in their molecular, metabolic and immune profiles."
Micah Donovan, PhD, instructor of Pharmacology and lead author on the study, said: "The number of discoveries produced by this analysis is spectacular. For example, this effort revealed the outsized effects of obesity in Down syndrome whereby individuals with obesity display strong changes in key hormonal circuits, metabolism and systemic inflammation." Srija Chilamcherla, MS, added: "We found strong biosignatures of immune dysregulation and cardiac stress that persist throughout life in those with a history of specific congenital heart defects. These results pave the way toward development of biomarkers that could help physicians monitor lifelong effects."
Angela Rachubinski, PhD, highlighted community involvement: "This is a clear example of the power of research participation and data sharing by the community. Thanks to contributions from research participants and their families we have gained much-needed knowledge about biological processes associated with co-occurring medical conditions more common in Down syndrome."
Michelle Sie Whitten, president and CEO at Global Down Syndrome Foundation, said: "This is another important breakthrough from our scientists at Crnic Institute that we hope will lead to more personalized care... We are proud GLOBAL's advocacy efforts led to establishment...of NIH-wide funding initiative INCLUDE Project which supports groundbreaking studies like this one."
