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.

中文翻译：

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肺动脉高压的遗传学和精确基因组学方法。


自第 6 届世界肺动脉高压研讨会以来，肺动脉高压 （PAH） 的基因组学取得了相当大的进展，在几个新基因中鉴定了罕见变异，以及导致 PAH 风险适度增加的常见变异。现在，由专家小组进行的基因和变异管理提供了一个强大的框架，用于了解要测试哪些基因以及如何在临床实践中解释变异。我们建议对有症状的 PAH 患者的特定亚组以及患有某些类型的 3 型肺动脉高压 （PH） 的儿童进行基因检测。对无症状家庭成员的检测以及在生殖决策中使用遗传学需要遗传学专家的参与。现在存在大量带有生物样本的 PAH 患者队列，并且已经开始扩展到非 1 组 PH。然而，这些群体主要来自欧洲;更大的多样性对于表征导致 PH 风险和治疗反应的基因组变异的全部范围至关重要。其他类型的组学数据也被纳入其中。此外，为了推进基因和通路特异性护理和靶向治疗，基因特异性登记对于支持患者及其家人并为遗传知情临床试验奠定基础至关重要。这将需要患者/家属、临床医生和研究人员之间的国际外展和合作。最终，患者来源的生物样本、临床和组学信息以及分析方法的协调将推动该领域的发展。