Principal Investigator: Dr Joseph Shieh
Department: University of California, San FranciscoTags: 53312, automated phenotype, cardiovascular disease, common variation, rare disease genetics, vascular dysplasia
Vascular dysplasias are conditions that cause blood vessels to develop in an unusual fashion. Individuals affected by these diseases can spontaneously bleed within a variety organ systems, including the lungs and brain. In some cases, the vessels can significantly alter the course through which blood flows within the body, resulting in life threatening complications like heart failure or pulmonary hypertension (high blood pressure within the vessels of the lungs).
These conditions tend to cluster within families, suggesting that children can inherit the diseases from their parents through their DNA. Indeed, the genetic cause in some patients has been precisely identified. These individuals possess a genetic change within a single gene involved in blood vessel development. That said, there are many individuals who possess the symptoms of a vascular dysplasia but do not have any of the known genetic alterations. We hypothesize that these (typically more mildly affected) patients have multiple weak genetic defects, which when added together, increase their risk for developing the disorder.
Our proposed project intends to use the UK Biobank to try and identify regions of the genome that likely contain one or more of these genetic alterations. We hope that it will discover new genes and molecular pathways involved in the pathogenesis of hereditary vascular dysplasias. Moreover, it should extend our knowledge of the disorders in general, providing new avenues of research into the prognosis, prevention and treatment of these important conditions.
Project extension – June 2020
To help validate our findings and the methodological approach in general, we will also conduct similar analyses on other rare vascular diseases (ex: Mafran syndrome), diseases affecting disparate sets of physiologic systems (ex: polycystic kidney disease, Diamond-Blackfan anemia, neurofibromatosis, and hereditary neuropathies) and on a genetic disorder with a well-characterized common variant architecture (alpha-1 antitrypsin deficiency).
Last updated Jun 22, 2020