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Study Description

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, Freeze 8 (GRCh38) and Freeze 9b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 8, Phases 1-4" and "TOPMed Whole Genome Sequencing Project - Freeze 9b, Phases 1-4". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

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.

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Publicly Available Data
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Study Inclusion/Exclusion Criteria

Inclusion: 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.

Study History

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.

Selected Publications
Diseases/Traits Related to Study (MeSH terms)
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Study Attribution
  • Principal Investigators
    • David A. Schwartz. University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
    • Tasha E. Fingerlin. National Jewish Health, Denver, CO, USA.
  • Funding Source
    • R01HL097163. National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, USA.