NHLBI GO-ESP: Family Studies (Familial Interstitial Pneumonia)

The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The Familial Interstitial Pneumonia (FIP) project seeks to identify genetic variants in coding regions of the human genome that are linked to FIP by examining the coding regions among relatives with FIP. These data will be used in conjunction with our other genetic studies to help us better understand how and why some individuals develop pulmonary fibrosis.]]>
Inclusion: Familial Interstitial Pneumonia (FIP) families qualify for this study after the evaluation described below identifies the presence of two or more cases of definite or probable idiopathic interstitial pneumonia (IIP) in individuals genetically related within three degrees. In at least one of these cases, the IIP diagnosis must be definite/probable idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP); requiring one case of IPF/UIP anchors the FIP families with the most common and severe form of IIP and creates consistency between the families. Exclusion: Because this is a study of genetic etiological factors in pulmonary fibrosis, we exclude subjects with: 1) medical conditions associated with the development of interstitial lung disease (ILD), including collagen vascular diseases; 2) clinically significant medication, drug, occupational, environmental, or avocational exposures known to be associated with the development of ILD; 3) known genetic diseases associated with ILD, such as Hermansky-Pudlak Syndrome, neurofibromatosis, tuberous sclerosis, Neimann-Pick disease, Gaucher's disease, and familial hypocalciuric hypercalcemia; and 4) cases of pulmonary fibrosis occurring in those less than 20 years of age. Although early onset cases are often considered to be valuable in genetic studies, it is very likely that cases of ILD occurring before age 20 do not represent pulmonary fibrosis and are likely to be etiologically different than cases of ILD in adults.]]>
We have been conducting a linkage study in Familial Interstitial Pneumonia (FIP) for over a decade. This was initially funded by an NHLBI grant (PI: DA Schwartz; U01 HL067467) and in 2005, when Dr. Schwartz became director of NIEHS, this project was funded by intramural research support (PI: DA Schwartz; Z01-ES101947). Since leaving the NIH, Dr. Schwartz has received two NHLBI grants (RO1-HL097163 and P01-HL092870) that support a GWAS and linkage study. Three sites were established to identify, enroll and phenotype subjects with FIP and their family members (National Jewish Health; Vanderbilt University; and Duke University Medical Center). Over the past decade, we have enrolled over 590 families with 2 or more cases of FIP, begun to phenotype 486 families and phenotyped/genotyped 82 of these families.]]>