NHLBI GO-ESP: Family Studies (Aortic Disease)

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. Acute aortic dissections are a common cause of premature death in the United States, ranking as high as the 15th leading cause of death. The goal of the Familial Thoracic Aortic Aneurysm and Dissection (TAAD) study at the University of Texas Health Science Center at Houston is to identify the genes causing thoracic aortic disease, and prevent premature deaths due to aortic dissections by identifying individuals who are genetically predisposed to the disease and initiating medical and surgical therapies to prevent dissections. In this study ("NHLBI GO-ESP Family Studies: Aortic Disease"), we have selected a series of families from the TAAD study, and are performing exome sequencing of 2 to 3 individuals per family.]]>
Inclusion Criteria: Participants who have a thoracic aortic aneurysm and/or dissection and a family history of the disease. Exclusion Criteria: Participants with known genetic syndromes or mutations causing thoracic aortic aneurysms or dissections.]]>
The Familial Thoracic Aortic Aneurysms and Dissection (TAAD) study at the University of Texas Health Science Center at Houston has recruited over 600 families with multiple members with thoracic aortic aneurysms and dissections. TAAD in these families is typically inherited in an autosomal dominant manner, with decreased penetrance particularly in women (familial disease is designated FTAAD). Families recruited into the research program demonstrate variable expression of TAAD, including varying age of disease onset, severity of presentation, and whether the TAA involves the aortic root or ascending aorta. Additional variability is evident with the identification of a subset of FTAAD families whose members experience aortic dissections with little to no enlargement of the ascending aorta, and families with large, stable aneurysms that are not prone to dissection. Additionally, clinical heterogeneity is apparent in the other features associated with TAAD in these families, such as intracranial aneurysms, iliac and popliteal artery aneurysms, occlusive vascular diseases (early onset strokes and coronary artery disease under the age of 55), abdominal aortic aneurysms, and patent ductus arteriosus. In this study ("NHLBI GO-ESP Family Studies: Aortic Disease"), we have selected a series of families from the TAAD study, and are performing exome sequencing of 2 to 3 individuals per family.]]>