1) Boston Early-Onset COPD Study: This study enrolls subjects with severe COPD (FEV1 < 40% predicted) at an early age (< 53 years) without alpha-1 antitrypsin deficiency (a known Mendelian risk factor for COPD). Extended pedigrees are enrolled, primarily in New England, although some more geographically distant subjects have been included. This study has been used for epidemiological studies, familial aggregation analysis, linkage analysis, and association analysis. DNA methylation studies have been performed in a subset of subjects. We were recently funded by the NIH to obtain whole exome sequences in more than 700 members of these pedigrees.
2) International COPD Genetics Network: This study enrolled sibships through a COPD proband at 10 clinical centers in the U.S. and Europe. This study has been used for epidemiological studies and association analysis. DNA methylation studies have been performed in a subset of subjects. We recently received NIH funding to obtain whole exome sequences in more than 300 members of these pedigrees.
3) National Emphysema Treatment Trial: NETT was a randomized clinical trial comparing lung volume reduction surgery to usual medical care. We received DNA samples from approximately 400 NETT participants. This study has been used for candidate gene and genome-wide association studies.
4) Normative Aging Study: NAS is a longitudinal study of more than 1,500 men who have been followed for more than 30 years. Genome-wide SNP genotyping was obtained on 400 healthy smoking controls. Multiple longitudinal biological samples have been collected in this population, which has regular health assessments including spirometry and other clinical tests. This study has been used for epidemiological studies and candidate gene association studies.
5) GENKOLS (Bergen, Norway) COPD Study: We have collaborated closely with investigators in Norway on the GENKOLS study of COPD. This study has been used for epidemiological analysis, candidate gene association studies, and genome-wide association studies.
6) ECLIPSE: This is a longitudinal study of COPD subjects and a small number of smoking control subjects that were followed regularly for 3 years, including 3 chest CT scans. This study has been used for epidemiological analyses and genome-wide association studies.
7) Transcontinental COPD Genetics Study: Severe COPD cases and healthy control subjects were enrolled in both Poland and Korea for genetic studies.
8) COPDGene: This is a large population of more than 10,000 smokers (1/3 African American and 2/3 non-Hispanic White) with chest CT scans and genome-wide SNP genotyping data. This study has been used for epidemiological analysis and genome-wide association studies.
1) CAMP: The Childhood Asthma Management Program (CAMP) is a longitudinal clinical trial of mild-to- moderate persistent asthma. A group of 1,041 children aged 5-12 at entry was initially followed for an average of 4.5 years and treated with asthma medications in three arms: nedocromil, budesonide, and as needed beta agonist. There are over 1,000 clinical phenotypic variables and the subjects have now been followed for 16 years. DNA and RNA samples are available on most subjects. Serum is also stored.
2) Costa Rica Asthma: Initially, 1,200 trios were collected to mirror the CAMP protocol and selection criteria. A set of 8 extended pedigrees were also collected, and both DNA and RNA on whole blood and serum are stored.
3) SHARP: This is a collection of asthmatic subjects from over 20 NHLBI asthma clinical trials in both children and adults. Extensive phenotypic data are available with treatment response, lung function, and medication use. Many subjects have bronchodilator and bronchoconstrictor testing. DNA is available on all and RNA on a subset through ABRIDGE. Serum is also available.
4) EVE: This is a collection of over 6,000 child and adult asthmatics from across the US. GWAS genotype data are available. DNA and RNA samples are available on a subset through ABRIDGE.
5) ABRIDGE: This population is a subset of EVE in which DNA and RNA were collected; most have CD4 cells stimulated and unstimulated with antigen. There are about 100 lung tissue RNA samples and 200 expectorated sputum RNA samples; all subjects have CD4 cells and whole blood RNA and DNA.
6) VDAART: This is a randomized controlled trial of vitamin D given to 900 pregnant women beginning between 12-18 weeks of pregnancy with follow-up of their children to see if they develop asthma. Longitudinal DNA and RNA have been collected on the mother and will be collected on the infant as well. Intestinal microbiome samples are being longitudinally collected. Multiple serum samples are available on both mother and infant.
7) Crimson: 16,000 asthmatics and matched controls with DNA samples on all subjects and detailed information from the electronic medical record at Partners Health Care. Useful for checking the relevance of any genetic findings in other populations and for assessing the relationship of genomics to health outcomes such as drug treatment, hospitalizations, and emergency room visits.
8) ALA Clinical Trials: DNA samples have been obtained on approximately 2,000 subjects participating in asthma clinical trials through the American Lung Association network.
9) VIVA: This is a birth cohort study of 10,000 mothers and their infants at a large HMO. The primary focus of the study is on maternal diet during pregnancy and its relationship to fetal outcomes such as hypertension, asthma, and obesity. DNA samples are available on a subset of about 5,000 subjects.
10) Home Allergens: This is a birth cohort of 1,000 mothers, fathers, and children followed from early pregnancy until age 16 to assess the relationship of early life allergen exposure on asthma development. Peripheral blood lymphocytes have been stimulated with a variety of environmental antigens and RNA obtained and cytokines have been measured on these samples. The environmental microbiome is also being measured.
11) Fetal Lung Development Tissues: Over 500 human fetal lung samples and over 1,000 mouse lung samples have had RNA extracted and arrayed to assess the gene expression signature of the developing fetal lung. While the human samples lack detailed information on most environmental exposures, all samples have had cotinine assayed to determine if mothers smoked during pregnancy and the effects of maternal smoking on the transcriptomic signature of the developing lung. DNA is also available and is being used to define the eQTLs of the developing lung.
12) Normal Controls: 400 normal age and gender-matched control subjects with GWAS and RNA have been screened to use as a comparison group for the family-based case data collected in CAMP and Costa Rica Asthma. The protocols for DNA, RNA and phenotyping are identical to what occurs in CAMP and Costa Rica.