Genetics and precision genomics approaches to pulmonary hypertension

Abstract

Considerable progress has been made in the genomics of pulmonary arterial hypertension (PAH) since the 6th World Symposium on Pulmonary Hypertension, with the identification of rare variants in several novel genes, as well as common variants that confer a modest increase in PAH risk. Gene and variant curation by an expert panel now provides a robust framework for knowing which genes to test and how to interpret variants in clinical practice. We recommend that genetic testing be offered to specific subgroups of symptomatic patients with PAH, and to children with certain types of group 3 pulmonary hypertension (PH). Testing of asymptomatic family members and the use of genetics in reproductive decision-making require the involvement of genetics experts. Large cohorts of PAH patients with biospecimens now exist and extension to non-group 1 PH has begun. However, these cohorts are largely of European origin; greater diversity will be essential to characterise the full extent of genomic variation contributing to PH risk and treatment responses. Other types of omics data are also being incorporated. Furthermore, to advance gene- and pathway-specific care and targeted therapies, gene-specific registries will be essential to support patients and their families and to lay the foundation for genetically informed clinical trials. This will require international outreach and collaboration between patients/families, clinicians and researchers. Ultimately, harmonisation of patient-derived biospecimens, clinical and omic information, and analytic approaches will advance the field.