NHLBI TOPMed: Pulmonary Fibrosis Whole Genome Sequencing

This is a set of cases diagnosed with idiopathic pulmonary fibrosis, a fatal interstitial lung disease. These cases were included in the TOPMed phase three studies. The planned study will compare these cases to within-TOPMed controls for genome-wide association studies.]]>
TOPMed Whole Genome Sequencing Methods: Freeze 9TOPMed Whole Genome Sequencing Methods: Freeze 10Inclusion: Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) and known or presumed European Ancestry. Cases may be familial (FIP) or sporadic (not known to be familial). Familial Interstitial Pneumonia (FIP) is defined as the presence of 2 or more cases of definite or probable Idiopathic Interstitial Pneumonia (IIP) in individuals genetically related within 3 degrees. In at least 1 of these cases, the IIP diagnosis must be definite/probable IPF/usual interstitial pneumonia (UIP). We include only those FIP subjects with IPF. Exclusion: 1) clinically significant medication, drug, occupational, environmental, or vocational exposures know to be associated with the development of interstitial lung disease; 2) systemic genetic diseases associated with interstitial lung disease (ILD); and 3) pulmonary fibrosis occurring in individuals less than 50 years of age.]]>
IPF is a complex genetic disorder that is associated with sequence changes in specific genes. We have previously found that genetic risk variants play major and similar roles in the development of both familial and sporadic IPF. In this proposal, we plan to definitively and comprehensively define the role of rare variants in the development of familial and sporadic IPF and explore how these rare variants interact with the strongest known etiologic factors for IPF (MUC5B promoter variant and cigarette smoking). We chose to focus on IPF in this proposal because IPF is the most common and severe fIIP, is a well-defined phenotype, affects 5 million worldwide, and is likely underdiagnosed. The findings from our previous research, as well as that of others, lead us to conclude that IPF is caused by rare, uncommon, and common variants in a number of risk genes that function alone and/or in concert to influence the risk of developing familial and sporadic forms of IPF, and that familial and sporadic IPF have a similar genetic etiology.]]>