NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Pulmonary Arterial Hypertension)

The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO.

The syndrome of pulmonary hypertension (PH) is a pulmonary disease that carries very high morbidity and mortality. Pulmonary \tarterial hypertension (PAH) is a category of PH (WHO Group 1) that includes several entities (idiopathic or heritable PAH, and PAH associated \twith other diseases such as connective tissue diseases including scleroderma-associated PAH) and carries a dismal prognosis, in particular \twhen it relates to scleroderma-associated PAH (median survival of about 4 years). It is believed that the severity of structural changes \tinvolving the pulmonary vasculature and right ventricular failure are genetically determined. The 'Genomics and Genetics of \tPulmonary Arterial Hypertension' study at Johns Hopkins University aims to identify genetic determinants associated with risk \tof PAH in a cohort of European American and African American participants with and without PAH. The study also focuses on patients \twith scleroderma, who are further stratified according to those who have or do not have PAH. The broad goals of the \tLung GO/ESP-GO falls into two general categories: (i) discovery of all variants (i.e., common and rare) in all protein-coding \tregions of the human genome (i.e., the exome) conferring risk to complex pulmonary diseases including PAH. The Johns Hopkins \tUniversity PAH cohort offers a unique opportunity to elucidate genetic variants that cause PAH.