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Clinical Genetics and Screening for Pulmonary Fibrosis

肺纤维化的临床遗传学和筛查

基本信息

批准号：
10542373
负责人：
GARY MATTHEW HUNNINGHAKE
金额：
$ 138.52万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10542373
关键词：
Acceleration Address Algorithms Awareness Biology Candidate Disease Gene Caring Chromosome Mapping Clinic Clinical Clinical Research Clinical Trials Data Detection Development Diagnosis Disease Disease Progression Early Diagnosis Environmental Exposure Ethnic Origin Ethnic Population First Degree Relative Future Genes Genetic Genetic Variation Genomic approach Genomics Goals Grant High Prevalence Interstitial Lung Diseases Length Lung Malignant Neoplasms Measures Medical Medical Genetics Medicine Methods Modeling Mucins Network-based Pathogenicity Patients Pharmacotherapy Physiological Play Population Population Heterogeneity Positioning Attribute Predictive Factor Predisposition Prevalence Process Prognosis Pulmonary Fibrosis Pulmonary function tests Registries Rejuvenation Relative Risks Reproducibility Risk Role Sample Size Site Test Result Therapeutic Intervention Trans-Omics for Precision Medicine Translational Research Validation Variant Work antifibrotic treatment biobank chest computed tomography clinical practice cohort college diagnostic value disorder risk early screening ethnic diversity exome experience fibrotic lung follow-up gene discovery gene network genetic information genetic testing genetic variant high risk idiopathic pulmonary fibrosis improved interest interstitial loss of function mortality multi-racial novel polygenic risk score proband prognostic value prognostication promoter public health priorities pulmonary function pulmonary function decline racial diversity racial population recruit risk prediction screening telomere transcriptomics

项目摘要

7. Project Summary The primary goal of this proposal is to develop an effective approach to screening for early stages of pulmonary fibrosis by assessing the diagnostic and prognostic value of clinical, environmental, genetic and genomic factors in at-risk relatives of patients with idiopathic pulmonary fibrosis (IPF). IPF, the most common and severe form of pulmonary fibrosis has a mortality rate comparable to that of many end-stage malignancies. Although IPF has historically been unresponsive to pharmacotherapy, recent studies have finally demonstrated that medical therapy can reduce the rate of decline in lung function, particularly when started early in the course of disease. In the prior grant cycle of this application we demonstrated that first-degree relatives were at high-risk to develop early stages of pulmonary fibrosis and that genetic testing helped to improve risk prediction. Based on these findings, we hypothesize that we will continue to observe a high prevalence of early pulmonary fibrosis in at-risk relatives; that we will be able to develop a clinically useful screening algorithm that combines key clinical, genetic, genomic, and environmental features for the early detection and prognostication of interstitial lung abnormalities (ILA) and/or pulmonary fibrosis in populations of diverse ethnic backgrounds; and that a subset of genes whose reduced expression predicts accelerated disease progression harbor pathogenic variants that help to drive this process. To assess these hypotheses, we propose the following Specific Aims: Aim 1) Develop an algorithm that can be used in clinical practice to identify relatives at the highest risk for pulmonary fibrosis, Aim 2) Prognosis: Define the baseline clinical, genetic, and genomic features in relatives found to have ILA that best predict their risk of disease progression, and 3) Identify novel genetic variants that contribute to pulmonary fibrosis susceptibility using an integrative genomics approach. In addition to providing a greater understanding of the role of that genetic variation plays in the development of IPF, the results from this study will motivate a clinical trial evaluating the use of screening and early therapeutic intervention in relatives at high-risk to develop IPF.

7. 项目总结