Completed Lungs & Breathing Heart, Stroke & Blood

National cohort study of idiopathic and heritable pulmonary arterial hypertension (renewal)

Funder BHF Charity-funded
Recipient organisation University of Cambridge
Funding £1.6M
Period Jan 2019 — Sept 2023

In plain English

AI plain-English summary

The UK National Cohort Study of Idiopathic and Heritable Pulmonary Arterial Hypertension has already sequenced the whole genomes of 863 UK patients and 392 European patients, and now seeks to continue tracking them over time. Pulmonary arterial hypertension is a rare but devastating disease where the arteries carrying blood from the heart to the lungs become narrowed, forcing the heart to work harder and eventually fail. Before this cohort was established in 2013, researchers lacked the large, well-characterised patient groups needed to identify the genetic causes of the disease and understand why some patients deteriorate faster than others. The project filled that gap by coupling genome sequencing with detailed clinical data and repeated blood samples. The research has already identified new genes that cause PAH and discovered blood-based biomarkers that predict patient outcomes. It also provided the evidence base to introduce genetic testing for PAH into the NHS. If continued, the cohort will enable long-term surveillance of patients and their relatives, track how the disease progresses over years, and serve as a platform for testing new therapies. For a rare disease where treatment options remain limited, this infrastructure could directly improve how patients are diagnosed, monitored, and treated.

View original technical description
In 2013, we established the UK National Cohort Study of Idiopathic and Heritable Pulmonary Arterial Hypertension (PAH) (www.ipahcohort.com) with funding from the British Heart Foundation. The rationale was that national collaboration and infrastructural support was critical to address major unanswered questions regarding the genetics, epidemiology, and clinical outcomes in this rare disease. We recruited 863 UK PAH patients (plus 392 from Europe) for whole genome sequencing as part of the NIHR Bioresource for Rare Diseases 10,000 genomes study, coupled to clinical information captured on dedicated data software (OpenClinica). Analysis of sequencing data identified rare causal variation in new genes for PAH, and common variant analysis identified novel loci for susceptibility and clinical outcomes. In addition, 617 patients have been recruited into longitudinal follow up with repeated data capture and sampling. Metabolomic and proteomic analyses revealed novel biomarkers for outcomes and new pathways implicated in pathobiology. Moreover, the PAH Cohort provided the route to introduce genetic testing for PAH to the NHS, and provided a platform for experimental medicine studies of new therapeutic agents. Based on the success and promise of this Cohort to transform our knowledge, classification and treatment of PAH we request follow-on funding to continue recruitment and long-term surveillance of patients and relatives.

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Researchers

Nicholas Morrell (EPMC Awardee)

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National cohort study of heritable pulmonary arterial hypertension
National Cohort Study of Idiopathic and Heritable Pulmonary Arterial Hypertension
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Original classification

Special Project

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