PURPOSE: Pulmonary fibrosis is a progressively fatal disease of unknown etiology. Increasing evidence suggests a genetic component to this disease. Understanding the genetic contribution enhances research to understand the cause and to develop effective treatments for this devastating disease.
METHODS: We analyzed the Utah Population Data Base, a unique computerized population-database which represents the Utah founder population and descendants and is linked to death certificates from 1904 to examine the familial clustering of individuals dying from Pulmonary Fibrosis. We identified 1,000 individuals who had at least 3 generations of genealogy data and whose death certificate listed Pulmonary Fibrosis as a cause of death (701 of these deaths occurred after 1989). We estimated the Relative Risk (RR) of death from Pulmonary Fibrosis among the first-, second-, and third-degree relatives of individuals dying from Pulmonary Fibrosis using rates estimated from all the linked death certificates. We also tested the hypothesis of no excess relatedness among the individuals dying from Pulmonary Fibrosis by comparing the average pairwise relatedness of all cases to the average pairwise relatedness of 1000 sets of matched controls.
RESULTS: We observed significantly increased risk for death from Pulmonary Fibrosis among the first- (RR = 4.69, 95% CI: 3.77, 5.77), second- (RR = 1.92, 95% CI: 1.43, 2.51), and third-degree relatives (RR = 1.14, 95% CI: 1.18, 1.70) of those dying from Pulmonary Fibrosis. The average relatedness of the 1,000 individuals dying from Pulmonary Fibrosis was significantly higher than the expected average relatedness estimated from 1,000 matched control sets (p<0.001). When close (first and second-degree) relationships were ignored, a significant excess relatedness was still observed.
CONCLUSION: Both the estimated RRs and the test for excess relatedness showed clustering in excess of expected among both close and distant relatives. This evidence provides strong support for a genetic contribution to death from Pulmonary Fibrosis.
CLINICAL IMPLICATIONS: Heritability of this disease should be considered in the evaluation of patients with pulmonary fibrosis.
DISCLOSURE: Mary Beth Scholand, No Financial Disclosure Information; No Product/Research Disclosure Information