In a groundbreaking new study published in Nature Communications, researchers from the University of Colorado Anschutz Linda Crnic Institute for Down Syndrome (Crnic Institute) discovered unique biological processes altered among individuals with Down syndrome who have different sets of co-occurring conditions. The findings mark an important step toward personalized treatment.
Biological differences are linked to co-occurring conditions of Down syndrome
The study is part of the ongoing Human Trisome Project ™, one of the largest and most comprehensive studies of people with Down syndrome, including extensive clinical data, multi-omics data sets and the largest biobank for the study of this condition to date. The Crnic Institute team analyzed hundreds of blood samples to identify physiological differences across research participants with Down syndrome who have histories of medical conditions that are more prevalent in this population. They mapped changes in gene expression, protein levels, metabolite abundance and immune cell types across 100 different clinical traits, producing an unprecedented atlas of the processes underlying variable medical complexity in Down syndrome.
"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, professor of Pharmacology, principal investigator of the Human Trisome Project and senior author of the paper. "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."
"The number of discoveries produced by this analysis is spectacular," said Micah Donovan, PhD, instructor of Pharmacology and a lead author of the study. "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."
The researchers used advanced computational tools to analyze the enormous volume of biological and clinical data generated through the study. The resulting dataset is expected to support many future investigations into the wide range of health outcomes experienced by people with Down syndrome.
"We found strong biosignatures of immune dysregulation and cardiac stress that persist throughout life in those with a history of specific congenital heart defects," explained Srija Chilamcherla, MS, another lead author of the study. "These results pave the way toward the development of biomarkers that could help physicians monitor the lifelong effects of medical conditions that occurred earlier in life."
The study team relied on a combination of self-reported medical histories and expert curation of medical records made available by self-advocates and their caregivers.
"This is a clear example of the power of research participation and data sharing by the community," said Angela Rachubinski, PhD, assistant research professor of Pediatrics and director of the Clinical and Translational Sciences Program at the Crnic Institute. "Thanks to the contributions from research participants and their families, we have gained much-needed knowledge about the biological processes associated with co-occurring medical conditions more common in Down syndrome."
Findings could enable future targeted therapies
The Crnic Institute study team has embarked on several follow-up studies aimed at accelerating the development of biomarkers of clinical utility and tailored therapeutic options for subsets of the Down syndrome population.
"This is another important breakthrough from our scientists at the Crnic Institute that we hope will lead to more personalized care and effective treatments for people with Down syndrome," said Michelle Sie Whitten, president and CEO of Global Down Syndrome Foundation (GLOBAL), a partner and an affiliate organization of the Crnic Institute. "As a mother of a brilliant 23-year-old with Down syndrome, I am eager to understand how this new knowledge may extend life and improve the health of millions of people with Down syndrome across the world. We are proud that GLOBAL's advocacy efforts with Congress and the National Institutes of Health (NIH) led to the establishment of the NIH-wide Down syndrome funding initiative, the INCLUDE Project, which supports groundbreaking studies and clinical trials like this one."
About the Linda Crnic Institute for Down Syndrome
The Linda Crnic Institute for Down Syndrome is one of the only academic research centers fully devoted to improving the lives of people with Down syndrome through advanced biomedical research spanning from basic science to translational and clinical investigations. Founded through the generous support and partnership of the Global Down Syndrome Foundation , the Anna and John J. Sie Foundation , and the University of Colorado , the Crnic Institute supports a thriving Down syndrome research program involving over 50 research teams across four campuses on the Colorado Front Range. To learn more, visit www.crnicinstitute.org or follow us on Facebook, Instagram, X, Bluesky and LinkedIn @CrnicInstitute.
About the University of Colorado Anschutz
The University of Colorado Anschutz is a world-class academic medical campus leading transformative advances in science, medicine, education and patient care. The campus includes the University of Colorado's health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado - which see nearly three million adult and pediatric patient visits each year. Innovative, interconnected and highly collaborative, CU Anschutz delivers life-changing treatments, exceptional patient care and top-tier professional training. The campus conducts world-renowned research supported by $890 million in funding, including $762 million in sponsored awards and $128 million in philanthropic gifts for research.
About Global Down Syndrome Foundation
The Global Down Syndrome Foundation (GLOBAL) is the largest nonprofit in the U.S. working to save lives and dramatically improve health outcomes for people with Down syndrome. GLOBAL established the first Down syndrome research institute and supports over 400 scientists and over 2,700 patients with Down syndrome from 40 states and 11 countries. Working closely with Congress and the National Institutes of Health, GLOBAL is the lead advocacy organization in the U.S. for Down syndrome research and care. GLOBAL has a membership of over 120 Down syndrome organizations worldwide and is part of a network of Affiliates – the Crnic Institute for Down Syndrome , the Sie Center for Down Syndrome , the University of Colorado Alzheimer's and Cognition Center – all on the Anschutz Medical Campus, and the GLOBAL Adult Down Syndrome Clinic at Denver Health.
GLOBAL's widely circulated medical publications include Global Medical Care Guidelines for Adults with Down Syndrome , Prenatal & Newborn Down Syndrome Information , and the award-winning magazine, Down Syndrome World TM . GLOBAL also organizes the annual AcceptAbility Gala in Washington D.C., and the annual Be Beautiful Be Yourself Fashion Show , the largest Down syndrome fundraiser in the world. Visit globaldownsyndrome.org
