About us
PAH-ICON was created to answer one of the biggest challenges in pulmonary hypertension (PH): understanding its genetic basis. No single centre has enough patients to do this alone.
Only international collaboration, bringing together thousands of patients with idiopathic and heritable pulmonary arterial hypertension (PAH), provides the statistical power needed to:
- to discover the complete genetic architecture of PAH
- to address the role of genetic variation in disease penetrance, phenotype and the clinical course of disease
- improve diagnosis and treatment outcomes
What we know so far
Research has already identified key genetic drivers of PAH:
- mutations in the bone morphogenetic protein type 2 receptor (BMPR2) account for 75% of cases of PAH that occurs in families, and 20% of apparently sporadic cases of idiopathic PAH
- mutations in additional BMPR2 pathways genes (ALK1, ENG, Smad1, Smad9), as well as mutations in KCNK3 (TASK1) and CAV-1 contribute a smaller proportion
- together these non-BMPR2 mutations account for less than 5% of PAH cases
- mutations in EIF2AK4 (GCN2) have emerged as the dominant cause of pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH).
However, much of the genetic basis of PAH remains unknown. Both rare and common genetic variation, alongside environmental factors, are likely to influence how the disease develops and progresses.
Our approach
PAH-ICON consists of a collaborative network of centres who share a common purpose, and who bring either research expertise and/or patient population. This collaborative approach enables research at a scale that no single centre could achieve.
The main questions we're working to answer:
- what is the prevalence of the known PAH genes in a large cohort?
- are the known PAH genes associated with specific clinical phenotypes?
- do the known PAH genes influence survival and response to therapy?
- what are the genetic determinants of penetrance in individuals harbouring BMPR2 mutations?
- what are the novel causal rare genetic variants associated with PAH?
- what is the contribution of common genetic variation to PAH and the clinical course of disease?
- what are the genetic contributions to intermediate phenotypes in PAH (e.g. metabolic and proteomic profiles)?
Global network of centres
PAH-ICON includes leading centres across Europe, North America, and beyond.
- Royal United Hospital, Bath
- University of Cambridge, Cambridge
- Royal Papworth Hospital, Cambridge
- Imperial College of Science, London
- St George’s Hospital, London
- King’s College London, London
- Royal Brompton Hospital, London
- Royal Free Hospital, London
- Great Ormond Street Hospital, London
- Freeman Hospital, Newcastle
- Royal Hallamshire Hospital, Sheffield
- Golden Jubilee Hospital, Glasgow
- Allegheny Health Network Institute, Pittsburgh
- University of Arizona, Tucson
- Cincinnati Children’s Hospital Medical Centre, Cincinnati
- Indiana University, Indianapolis
- Columbia University, New York
- Intermountain Medical Center, Utah
- Vanderbilt University Medical Center, Nashville
- The Johns Hopkins University, Maryland
- Leland Stanford Junior University, California
"Only global collaboration at scale can answer the key questions about how genetics shapes PAH"
Want to get involved?
If you’re a basic or clinician scientist interested in P(A)H genetics, we would love to hear from you.