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1. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author

Tejwani, Vickram, Fawzy, Ashraf, Putcha, Nirupama, Castaldi, Peter J, Cho, Michael H, Pratte, Katherine A, Bhatt, Surya P, Lynch, David A, Humphries, Stephen M, Kinney, Gregory L, D’Alessio, Franco R, Hansel, Nadia N, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bramvan, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Young, Kendra A, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Pernicano, Perry G, Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, and Guy, Elizabeth

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Emphysema, Lung, Tobacco, Chronic Obstructive Pulmonary Disease, Tobacco Smoke and Health, Cancer, Respiratory, Aged, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Cohort Studies, Disease Progression, Female, Forced Expiratory Volume, Humans, Lung Volume Measurements, Male, Middle Aged, Prospective Studies, Protective Factors, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Spirometry, Tomography, X-Ray Computed, Vital Capacity, Walk Test, angiotensin II, COPD, emphysema progression, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAttenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers.Research questionIs use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema?MethodsFormer and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume

Published
2021

2. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Chandra, Divay, Gupta, Aman, Kinney, Gregory L, Fuhrman, Carl R, Leader, Joseph K, Diaz, Alejandro A, Bon, Jessica, Barr, R Graham, Washko, George, Budoff, Matthew, Hokanson, John, Sciurba, Frank C, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Boueiz, Adel R, Castaldi, Peter J, Cho, Michael, DeMeo, Dawn L, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Al Qaisi, Mustafa, Coxson, Harvey O, Gray, Teresa, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Newell, John D, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Wilson, Carla G, Jensen, Robert, Crooks, Jim, Everett, Douglas, Moore, Camille, Strand, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Bhatt, Surya, Martinez, Carlos, Murray, Susan, Soler, Xavier, Banaei-Kashani, Farnoush, Bowler, Russell P, Kechris, Katerina, Curtis, Jeffrey L, Pernicano, Perry G, Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, and Parulekar, Amit

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Lung, Heart Disease, Prevention, Atherosclerosis, Heart Disease - Coronary Heart Disease, Chronic Obstructive Pulmonary Disease, Emphysema, Tobacco Smoke and Health, Biomedical Imaging, Tobacco, Cardiovascular, Clinical Research, Respiratory, Good Health and Well Being, Airway Obstruction, Airway Remodeling, Asymptomatic Diseases, Biological Variation, Population, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, Middle Aged, Organ Size, Plethysmography, Pulmonary Emphysema, Respiratory Function Tests, Risk Factors, Smoking, Tomography, X-Ray Computed, United States, COPD, coronary artery disease, lung hyperinflation, smoking, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundSmokers manifest varied phenotypes of pulmonary impairment.Research questionWhich pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers?Study design and methodsWe analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV1 to FVC ratio, < 0.70).ResultsPulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV1 and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts.InterpretationLung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV1 and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Published
2021

3. Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.

Author

Somineni, Hari, Nagpal, Sini, Venkateswaran, Suresh, Cutler, David, Okou, David, Haritunians, Talin, Simpson, Claire, Begum, Ferdouse, Datta, Lisa, Quiros, Antonio, Seminerio, Jenifer, Mengesha, Emebet, Alexander, Jonathan, Baldassano, Robert, Dudley-Brown, Sharon, Cross, Raymond, Dassopoulos, Themistocles, Denson, Lee, Dhere, Tanvi, Iskandar, Heba, Dryden, Gerald, Hou, Jason, Hussain, Sunny, Hyams, Jeffrey, Isaacs, Kim, Kader, Howard, Kappelman, Michael, Katz, Jeffry, Kellermayer, Richard, Kuemmerle, John, Lazarev, Mark, Li, Ellen, Mannon, Peter, Moulton, Dedrick, Newberry, Rodney, Patel, Ashish, Pekow, Joel, Saeed, Shehzad, Valentine, John, Wang, Ming-Hsi, McCauley, Jacob, Abreu, Maria, Jester, Traci, Molle-Rios, Zarela, Palle, Sirish, Scherl, Ellen, Kwon, John, Rioux, John, Duerr, Richard, Silverberg, Mark, Zwick, Michael, Stevens, Christine, Daly, Mark, Cho, Judy, Gibson, Greg, McGovern, Dermot, Brant, Steven, and Kugathasan, Subra

Subjects
CALB2, PTGER4, differential genetic architecture, polygenic risk scores, rare variants, trans-ethnic comparative analysis, understudied populations, whole-genome sequencing of African Americans, Black or African American, Aged, Aged, 80 and over, Calbindin 2, Colitis, Ulcerative, Crohn Disease, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inflammatory Bowel Diseases, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Receptors, Prostaglandin E, EP4 Subtype, White People, Whole Genome Sequencing
Abstract

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

Published
2021

4. Machine Learning Characterization of COPD Subtypes Insights From the COPDGene Study

Author

Castaldi, Peter J, Boueiz, Adel, Yun, Jeong, San Jose Estepar, Raul, Ross, James C, Washko, George, Cho, Michael H, Hersh, Craig P, Kinney, Gregory L, Young, Kendra A, Regan, Elizabeth A, Lynch, David A, Criner, Gerald J, Dy, Jennifer G, Rennard, Stephen I, Casaburi, Richard, Make, Barry J, Crapo, James, Silverman, Edwin K, Hokanson, John E, Crapo, James D, Beaty, Terri, Begum, Ferdouse, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hetmanski, Jacqueline, Hobbs, Brian D, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Bhatt, Surya P, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Soler, Xavier, Bowler, Russell P, and Kechris, Katerina

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Lung, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Cluster Analysis, Diagnostic Imaging, Disease Progression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Machine Learning, Molecular Epidemiology, Phenotype, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, COPD, emphysema, machine learning, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

Published
2020

6. De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population

Author

Kessler, Michael D, Loesch, Douglas P, Perry, James A, Heard-Costa, Nancy L, Taliun, Daniel, Cade, Brian E, Wang, Heming, Daya, Michelle, Ziniti, John, Datta, Soma, Celedón, Juan C, Soto-Quiros, Manuel E, Avila, Lydiana, Weiss, Scott T, Barnes, Kathleen, Redline, Susan S, Vasan, Ramachandran S, Johnson, Andrew D, Mathias, Rasika A, Hernandez, Ryan, Wilson, James G, Nickerson, Deborah A, Abecasis, Goncalo, Browning, Sharon R, Zöllner, Sebastian, O’Connell, Jeffrey R, Mitchell, Braxton D, Lung, and Blood Institute Trans-Omics for Precision Medicine Consortium National Heart, Group, TOPMed Population Genetics Working, O’Connor, Timothy D, Aalbers, Sanne, Abdalla, Moustafa, Abdul-Rahman, Omar, Abecasis, Gonçalo, Abhyankar, Avinash, Adrianto, Indra, Aguet, Francois, Akers, Rachel, Al-Tobasei, Rafet, Albert, Christine, Aldred, Micheala, Almasy, Laura, Almeida, Marcio, Alonso, Alvaro, Ament, Seth, Ampleford, Elizabeth, An, Ping, Anderson, Christopher D, Andersson, Charlotte, Anugu, Pramod, Appelbaum, Elizabeth, Ardlie, Kristin, Arking, Dan, Armasu, Sebastian M, Arnett, Donna K, Arruda, Heather, Arvanitis, Marios, Ashley-Koch, Allison, Ashrani, Aneel, Aslibekyan, Stella, Assimes, Tim, Atkinson, Elizabeth, Auer, Paul, Austin, Thomas R, Avery, Christy, Avila-Pacheco, Julian, Avillach, Paul, Aviv, Abraham, Avramopoulos, Dimitrios, Ballantyne, Christie, Balte, Pallavi, Bamshad, Michael, Bancks, Mike, Barnard, John, Barr, R Graham, Barron-Casella, Emily, Bartz, Traci, Barwick, Lucas, Basu, Saonli, Battle, Alexis, Baumann, Michael, Beame, David, Beaty, Terri, Beck, Gerald, Becker, Lewis, Becker, Diane, Beer, Rebecca, Begum, Ferdouse, Beiser, Alexa, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Berk-Rauch, Hanna, Besich, Zachary M, Bezerra, Marcos, Bhatt, Surya, Bi, Wenjian, Bick, Alexander, and Bielak, Larry

Subjects
Biological Sciences, Genetics, Biotechnology, Human Genome, Precision Medicine, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Amish, Cohort Studies, DNA Mutational Analysis, Female, Genetics, Population, Genome, Human, Heterozygote, Humans, Male, Mutation, Pedigree, Whole Genome Sequencing, Young Adult, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group, de novo mutations, diversity, mutation rate, recombination
Abstract

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains

Published
2020

7. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

Author

Young, Alexandra L, Bragman, Felix JS, Rangelov, Bojidar, Han, MeiLan K, Galbán, Craig J, Lynch, David A, Hawkes, David J, Alexander, Daniel C, Hurst, John R, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Qiao, Dandi, Wan, Emily S, Won, Sungho, Sakornsakolpat, Phuwanat, Prokopenko, Dmitry, Al Qaisi, Mustafa, Coxson, Harvey O, Gray, Teresa, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Newell, John D, Ross, James C, Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Bhatt, Surya, Bon, Jessica, Martinez, Carlos, Murray, Susan, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Barr, R Graham, Austin, John, D’Souza, Belinda, Pearson, Gregory DN, Rozenshtein, Anna, Thomashow, Byron, MacIntyre, Neil, McAdams, H Page, Washington, Lacey, McEvoy, Charlene, and Tashjian, Joseph

Subjects
Biomedical Imaging, Lung, Clinical Research, Chronic Obstructive Pulmonary Disease, Aetiology, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Respiratory, Aged, Disease Progression, Female, Humans, Male, Middle Aged, Models, Theoretical, Pulmonary Disease, Chronic Obstructive, Tomography, X-Ray Computed, clustering, CT imaging, emphysema, bronchitis, chronic obstructive pulmonary disease, COPDGene Investigators, Medical and Health Sciences, Respiratory System
Abstract

Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P

Published
2020

8. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Biotechnology, Genetics, Lung, Pediatric, Human Genome, Clinical Research, Asthma, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Cell Adhesion Molecules, Child, Child, Preschool, Costa Rica, Female, Forced Expiratory Volume, Humans, Interferon Regulatory Factors, Male, Middle Aged, Respiratory Physiological Phenomena, Vital Capacity, Whole Genome Sequencing, Young Adult, airway hyperresponsiveness, asthma, lung function, whole genome sequencing, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

9. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Author

Yun, Jeong H, Lamb, Andrew, Chase, Robert, Singh, Dave, Parker, Margaret M, Saferali, Aabida, Vestbo, Jørgen, Tal-Singer, Ruth, Castaldi, Peter J, Silverman, Edwin K, Hersh, Craig P, Crapo, James D, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Busch, Robert, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hansel, Nadia N, Hardin, Megan E, Hayden, Lystra P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Qiao, Dandi, Santorico, Stephanie, Silverman, E, Wan, Emily S, Won, Sungho, Qaisi, Mustafa Al, Coxson, Harvey O, Gray, Teresa, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Newell, John D, Ross, James C, San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Hersh, Craig, Barr, R Graham, Austin, John, D'Souza, Belinda, Pearson, Gregory DN, and Rozenshtein, Anna

Subjects
Lung, Chronic Obstructive Pulmonary Disease, Clinical Research, Respiratory, Aged, Disease Progression, Eosinophils, Female, Humans, Leukocyte Count, Longitudinal Studies, Male, Middle Aged, Observational Studies as Topic, Pulmonary Disease, Chronic Obstructive, Chronic obstructive pulmonary disease, asthma, eosinophil, exacerbation, COPDGene and ECLIPSE Investigators, Immunology, Allergy
Abstract

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n = 1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n = 1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Published
2018

10. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author

Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S., Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O., Galban, Craig J., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Nardelli, Pietro, Newell, John D., Jr., Notary, Aleena, Oh, Andrea, Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bramvan, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R., Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Young, Kendra A., Bhatt, Surya P., Bon, Jessica, Diaz, Alejandro A., Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Bowler, Russell P., Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L., Pernicano, Perry G., Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, Hersh, Craig, Washko, George, Barr, R. Graham, Austin, John, D’Souza, Belinda, Thomashow, Byron, MacIntyre, Neil, Jr., McAdams, H. Page, Washington, Lacey, Flenaugh, Eric, Terpenning, Silanth, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Hansel, Nadia N., Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Kunisaki, KenM., Bowler, Russell, Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Conrad, Douglas, Yen, Andrew, Comellas, Alejandro P., Hoth, Karin F., Newell, John, Jr., Thompson, Brad, Kazerooni, Ella, Labaki, Wassim, Galban, Craig, Vummidi, Dharshan, Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Chandra, Divay, Fuhrman, Carl, Weissfeld, Joel, Tejwani, Vickram, Fawzy, Ashraf, Cho, Michael H., Pratte, Katherine A., Humphries, Stephen M., Kinney, Gregory L., and D’Alessio, Franco R.

Published
2021
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11. Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression

Author

Boueiz, Adel, Chang, Yale, Cho, Michael H, Washko, George R, San José Estépar, Raul, Bowler, Russell P, Crapo, James D, DeMeo, Dawn L, Dy, Jennifer G, Silverman, Edwin K, Castaldi, Peter J, Crapo, James, Silverman, Edwin, Make, Barry, Regan, Elizabeth, Beaty, Terri, Laird, Nan, Lange, Christoph, Santorico, Stephanie, Hokanson, John, DeMeo, Dawn, Hansel, Nadia, Hersh, Craig, Castaldi, Peter, McDonald, Merry-Lynn, Wan, Emily, Hardin, Megan, Hetmanski, Jacqueline, Parker, Margaret, Foreman, Marilyn, Hobbs, Brian, Busch, Robert, Qiao, Dandi, Halper-Stromberg, Eitan, Begum, Ferdouse, Won, Sungho, Lutz, Sharon, Lynch, David A, Coxson, Harvey O, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Newell, John D, Ross, James C, Estépar, Raul José, Stoel, Berend C, Tschirren, Juerg, van Rikxoort, Eva, van Ginneken, Bram, Wilson, Carla G, Qaisi, Mustafa Al, Gray, Teresa, Kluiber, Alex, Mann, Tanya, Sieren, Jered, Stinson, Douglas, Schroeder, Joyce, Van Beek, Edwin, Jensen, Robert, Everett, Douglas, Faino, Anna, Strand, Matt, Wilson, Carla, Hokanson, John E, Kinney, Gregory, Young, Kendra, Pratte, Katherine, Duca, Lindsey, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Bandi, Venkata, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, Nachiappan, Arun, Jacobson, Francine, Barr, R Graham, Thomashow, Byron, Austin, John, D’Souza, Belinda, and Pearson, Gregory DN

Subjects
Clinical Research, Chronic Obstructive Pulmonary Disease, Lung, Emphysema, Prevention, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Aged, Comorbidity, Disease Progression, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Pulmonary Emphysema, Severity of Illness Index, Tomography, X-Ray Computed, clustering, COPD, COPD disease progression, emphysema distribution, machine learning, COPDGene Investigators, Clinical Sciences, Respiratory System
Abstract

BackgroundEmphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized.MethodsWe sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared.ResultsThree clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted.ConclusionsSubgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Published
2018

12. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Boueiz, Adel R., Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S., Won, Sungho, Al Qaisi, Mustafa, Coxson, Harvey O., Gray, Teresa, Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Newell, John D., Jr., Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, Ginneken, Bram van, van Rikxoort, Eva, Washko, George, Wilson, Carla G., Jensen, Robert, Crooks, Jim, Everett, Douglas, Moore, Camille, Strand, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A., Bhatt, Surya, Bon, Jessica, Martinez, Carlos, Murray, Susan, Soler, Xavier, Banaei-Kashani, Farnoush, Bowler, Russell P., Kechris, Katerina, Curtis, Jeffrey L., Pernicano, Perry G., Hanania, Nicola, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, Diaz, Alejandro A., Hersh, Craig, Barr, R. Graham, Austin, John, D’Souza, Belinda, Thomashow, Byron, MacIntyre, Neil, Jr., McAdams, H. Page, Washington, Lacey, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Hansel, Nadia N., Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, DeBakey, Michael E., Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Kunisaki, Ken M., Berkowitz, Eugene, Westney, Gloria, Bowler, Russell, Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya P., Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Ramsdell, Joe, Friedman, Paul, Yen, Andrew, Comellas, Alejandro P., Hoth, Karin F., Newell, John, Jr., Thompson, Brad, Kazerooni, Ella, Martinez, Carlos H., Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Chandra, Divay, Fuhrman, Carl, Weissfeld, Joel, Anzueto, Antonio, Adams, Sandra, Maselli-Caceres, Diego, Ruiz, Mario E., Gupta, Aman, Kinney, Gregory L., Fuhrman, Carl R., Leader, Joseph K., Hokanson, John, and Sciurba, Frank C.

Published
2021
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13. Machine Learning Characterization of COPD Subtypes: Insights From the COPDGene Study

Author

Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Prokopenko, Dmitry, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S., Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O., Galban, Craig J., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Nardelli, Pietro, Newell, John D., Jr., Notary, Aleena, Oh, Andrea, Ross, James C., Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R., Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Young, Kendra A., Bhatt, Surya P., Bon, Jessica, Diaz, Alejandro A., Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Bowler, Russell P., Kechris, Katerina, Banaei-Kashani, Farnoush, Boueiz, Adel, Yun, Jeong, Washko, George, Cho, Michael H., Kinney, Gregory L., Criner, Gerald J., Dy, Jennifer G., Rennard, Stephen I., Casaburi, Richard, and Crapo, James

Published
2020
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14. Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

Author

Brant, Steven, Okou, David, Simpson, Claire, Cutler, David, Haritunians, Talin, Bradfield, Jonathan, Chopra, Pankaj, Prince, Jarod, Begum, Ferdouse, Kumar, Archana, Huang, Chengrui, Venkateswaran, Suresh, Datta, Lisa, Wei, Zhi, Thomas, Kelly, Herrinton, Lisa, Klapproth, Jan-Micheal, Quiros, Antonio, Seminerio, Jenifer, Liu, Zhenqiu, Alexander, Jonathan, Baldassano, Robert, Dudley-Brown, Sharon, Cross, Raymond, Dassopoulos, Themistocles, Denson, Lee, Dhere, Tanvi, Dryden, Gerald, Hanson, John, Hou, Jason, Hussain, Sunny, Hyams, Jeffrey, Isaacs, Kim, Kader, Howard, Kappelman, Michael, Katz, Jeffry, Kellermayer, Richard, Kirschner, Barbara, Kuemmerle, John, Kwon, John, Lazarev, Mark, Li, Ellen, Mack, David, Mannon, Peter, Moulton, Dedrick, Newberry, Rodney, Osuntokun, Bankole, Patel, Ashish, Saeed, Shehzad, Targan, Stephan, Valentine, John, Wang, Ming-Hsi, Zonca, Martin, Rioux, John, Duerr, Richard, Silverberg, Mark, Cho, Judy, Hakonarson, Hakon, Zwick, Michael, McGovern, Dermot, and Kugathasan, Subra

Subjects
Genetic Analysis, Risk Factor, SNP, Trans-Ethnic, Adenylyl Cyclases, Black or African American, Case-Control Studies, Cell Adhesion Molecules, Neuronal, Colitis, Ulcerative, Crohn Disease, GPI-Linked Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Interleukin-12 Subunit p40, KCNQ2 Potassium Channel, Polymorphism, Single Nucleotide, Receptors, CXCR6, Receptors, Chemokine, Receptors, Interleukin, Receptors, Prostaglandin E, EP4 Subtype, Receptors, Virus, Repressor Proteins, Sorting Nexins, Tenascin, Ubiquitin Thiolesterase, White People
Abstract

BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohns disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P

Published
2017

15. Common and Rare Variants Genetic Association Analysis of Cigarettes per Day Among Ever-Smokers in Chronic Obstructive Pulmonary Disease Cases and Controls

Author

ECLIPSE and COPDGene Investigators, Lutz, Sharon M., Frederiksen, Brittni, Begum, Ferdouse, McDonald, Merry-Lynn N., Cho, Michael H., Hobbs, Brian D., Parker, Margaret M., DeMeo, Dawn L., Hersh, Craig P., Ehringer, Marissa A., Young, Kendra, Jiang, Lai, Foreman, Marilyn G., Kinney, Greg L., Make, Barry J., Lomas, David A., Bakke, Per, Gulsvik, Amund, Crapo, James D., Silverman, Edwin K., Beaty, Terri H., and Hokanson, John E.

Published
2019

16. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, Zoellner, Sebastian, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Levin, Albert M., Gui, Hongsheng, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Weiss, Scott T., and Lasky-Su, Jessica A.

Published
2019
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17. The St. George’s Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

Author

Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Busch, Robert, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hansel, Nadia N., Hardin, Megan E., Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Qiao, Dandi, Santorico, Stephanie, Wan, Emily S., Won, Sungho, Charbonnier, Jean-Paul, Coxson, Harvey O., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Newell, John D., Jr., Ross, James C., San Jose Estepar, Raul, Sieren, Jered, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A., Curtis, Jeffrey L., Martinez, Carlos H., Pernicano, Perry G., Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Hersh, Craig, Barr, R. Graham, Austin, John, D’Souza, Belinda, Pearson, Gregory D.N., Rozenshtein, Anna, Thomashow, Byron, MacIntyre, Neil, Jr., McAdams, H. Page, Washington, Lacey, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Berkowitz, Eugene, Flenaugh, Eric L., Westney, Gloria, Bowler, Russell, Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya, Iyer, Anand, Nath, Hrudaya, Oates, Gabriela, Sonavane, Sushil, Wells, J. Michael, Ramsdell, Joe, Friedman, Paul, Soler, Xavier, Yen, Andrew, Comellas, Alejandro P., Newell, John, Jr., Thompson, Brad, Kazerooni, Ella, Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Bon, Jessica, Chandra, Divay, Fuhrman, Carl, Weissfeld, Joel, Anzueto, Antonio, Adams, Sandra, Maselli-Caceres, Diego, Ruiz, Mario E., Zhao, Huaqing, Regan, Elizabeth, Jones, Paul W., and Criner, Gerard J.

Published
2019
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18. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Author

Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Busch, Robert, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hansel, Nadia N., Hardin, Megan E., Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Qiao, Dandi, Santorico, Stephanie, Wan, Emily S., Won, Sungho, Al Qaisi, Mustafa, Coxson, Harvey O., Gray, Teresa, Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Newell, John D., Jr., Ross, James C., San Jose Estepar, Raul, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G., Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A., Curtis, Jeffrey L., Martinez, Carlos H., Pernicano, Perry G., Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Hersh, Craig, Barr, R. Graham, Austin, John, D'Souza, Belinda, Pearson, Gregory D.N., Rozenshtein, Anna, Thomashow, Byron, MacIntyre, Neil, Jr., McAdams, H. Page, Washington, Lacey, McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Horton, Karen, Lambert, Allison, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Budoff, Matthew, Fischer, Hans, Porszasz, Janos, Rossiter, Harry, Stringer, William, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Berkowitz, Eugene, Westney, Gloria, Bowler, Russell, Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D'Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, Mamary, A. James, Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Bhatt, Surya, Iyer, Anand, Nath, Hrudaya, Wells, J. Michael, Ramsdell, Joe, Friedman, Paul, Soler, Xavier, Yen, Andrew, Comellas, Alejandro P., Newell, John, Jr., Thompson, Brad, Kazerooni, Ella, Billings, Joanne, Begnaud, Abbie, Allen, Tadashi, Sciurba, Frank, Bon, Jessica, Chandra, Divay, Fuhrman, Carl, Weissfeld, Joel, Anzueto, Antonio, Adams, Sandra, Maselli-Caceres, Diego, Ruiz, Mario E., Ivanov, Y., Kostov, K., Bourbeau, J., Fitzgerald, M., Hernandez, P., Killian, K., Levy, R., Maltais, F., O'Donnell, D., Krepelka, J., Vestbo, J., Wouters, E., Quinn, D., Bakke, P., Kosnik, M., Agusti, A., Sauleda, J., de Mallorca, P., Feschenko, Y., Gavrisyuk, V., Kiev, L. Yashina, Monogarova, N., Calverley, P., Lomas, D., MacNee, W., Singh, D., Wedzicha, J., Anzueto, A., Braman, S., Casaburi, R., Celli, B., Giessel, G., Gotfried, M., Greenwald, G., Hanania, N., Mahler, D., Make, B., Rennard, S., Rochester, C., Scanlon, P., Schuller, D., Sciurba, F., Sharafkhaneh, A., Siler, T., Silverman, E., Wanner, A., Wise, R., ZuWallack, R., Coxson, H., Crim, C., Edwards, L., Singer, R. Tal, Yates, J., Miller, B., Tal-Singer, R., Yun, Jeong H., Lamb, Andrew, Chase, Robert, Singh, Dave, Saferali, Aabida, Vestbo, Jørgen, and Tal-Singer, Ruth

Published
2018
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19. Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study

Author

Crapo, James D., Make, Barry J., Regan, Elizabeth A., Silverman, Edwin K., Beaty, Terri, Begum, Ferdouse, Boueiz, Adel R., Busch, Robert, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Foreman, Marilyn G., Halper-Stromberg, Eitan, Hansel, Nadia N., Hardin, Megan E., Hayden, Lystra P., Hersh, Craig P., Hetmanski, Jacqueline, Hobbs, Brian D., Hokanson, John E., Laird, Nan, Lange, Christoph, Lutz, Sharon M., McDonald, Merry-Lynn, Parker, Margaret M., Qiao, Dandi, Santorico, Stephanie, Wan, Emily S., Al Qaisi, Mustafa, Coxson, Harvey O., Gray, Teresa, Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Kluiber, Alex, Lynch, David A., Newell, John D., Jr., Ross, James C., Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C., Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G., Jensen, Robert, Crooks, Jim, Everett, Douglas, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A., Qiu, Weiliang, Strand, Matthew J., and van Beek, Edwin J.

Published
2018
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20. Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression

Author

Crapo, James, Silverman, Edwin, Make, Barry, Regan, Elizabeth, Beaty, Terri, Laird, Nan, Lange, Christoph, Cho, Michael H., Santorico, Stephanie, Hokanson, John, DeMeo, Dawn, Hansel, Nadia, Hersh, Craig, Castaldi, Peter, McDonald, Merry-Lynn, Wan, Emily, Hardin, Megan, Hetmanski, Jacqueline, Parker, Margaret, Foreman, Marilyn, Hobbs, Brian, Busch, Robert, Boueiz, Adel, Qiao, Dandi, Halper-Stromberg, Eitan, Begum, Ferdouse, Won, Sungho, Lutz, Sharon, Lynch, David A., Coxson, Harvey O., Han, MeiLan K., Hoffman, Eric A., Humphries, Stephen, Jacobson, Francine L., Judy, Philip F., Kazerooni, Ella A., Newell, John D., Jr., Ross, James C., Estépar, Raul José, Stoel, Berend C., Tschirren, Juerg, Rikxoort, Eva van, van Ginneken, Bram, Washko, George R., Wilson, Carla G., Qaisi, Mustafa Al, Gray, Teresa, Kluiber, Alex, Mann, Tanya, Sieren, Jered, Stinson, Douglas, Schroeder, Joyce, Beek, Edwin Van, Jensen, Robert, Everett, Douglas, Faino, Anna, Strand, Matt, Wilson, Carla, Hokanson, John E., Kinney, Gregory, Young, Kendra, Pratte, Katherine, Duca, Lindsey, Curtis, Jeffrey L., Martinez, Carlos H., Pernicano, Perry G., Hanania, Nicola, Alapat, Philip, Bandi, Venkata, Atik, Mustafa, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Parulekar, Amit, Nachiappan, Arun, Jacobson, Francine, Graham Barr, R., Thomashow, Byron, Austin, John, D’Souza, Belinda, Pearson, Gregory D.N., Rozenshtein, Anna, MacIntyre, Neil, Jr., Washington, Lacey, Page McAdams, H., McEvoy, Charlene, Tashjian, Joseph, Wise, Robert, Brown, Robert, Horton, Karen, Putcha, Nirupama, Casaburi, Richard, Adami, Alessandra, Porszasz, Janos, Fischer, Hans, Budoff, Matthew, Rossiter, Harry, Sharafkhaneh, Amir, Lan, Charlie, Wendt, Christine, Bell, Brian, Westney, Gloria, Berkowitz, Eugene, Bowler, Russell, Lynch, David, Rosiello, Richard, Pace, David, Criner, Gerard, Ciccolella, David, Cordova, Francis, Dass, Chandra, D’Alonzo, Gilbert, Desai, Parag, Jacobs, Michael, Kelsen, Steven, Kim, Victor, James Mamary, A., Marchetti, Nathaniel, Satti, Aditi, Shenoy, Kartik, Steiner, Robert M., Swift, Alex, Swift, Irene, Vega-Sanchez, Maria Elena, Dransfield, Mark, Bailey, William, Michael Wells, J., Bhatt, Surya, Nath, Hrudaya, Ramsdell, Joe, Friedman, Paul, Soler, Xavier, Yen, Andrew, Cornellas, Alejandro, Newell, John, Jr., Thompson, Brad, Han, MeiLan, Kazerooni, Ella, Martinez, Carlos, Billings, Joanne, Allen, Tadashi, Sciurba, Frank, Chandra, Divay, Weissfeld, Joel, Fuhrman, Carl, Bon, Jessica, Anzueto, Antonio, Adams, Sandra, Maselli-Caceres, Diego, Ruiz, Mario E., Chang, Yale, San José Estépar, Raul, Bowler, Russell P., Crapo, James D., DeMeo, Dawn L., Dy, Jennifer G., Silverman, Edwin K., and Castaldi, Peter J.

Published
2018
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21. Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci

Author

Leslie, Elizabeth J., Taub, Margaret A., Liu, Huan, Steinberg, Karyn Meltz, Koboldt, Daniel C., Zhang, Qunyuan, Carlson, Jenna C., Hetmanski, Jacqueline B., Wang, Hang, Larson, David E., Fulton, Robert S., Kousa, Youssef A., Fakhouri, Walid D., Naji, Ali, Ruczinski, Ingo, Begum, Ferdouse, Parker, Margaret M., Busch, Tamara, Standley, Jennifer, Rigdon, Jennifer, Hecht, Jacqueline T., Scott, Alan F., Wehby, George L., Christensen, Kaare, Czeizel, Andrew E., Deleyiannis, Frederic W.-B., Schutte, Brian C., Wilson, Richard K., Cornell, Robert A., Lidral, Andrew C., Weinstock, George M., Beaty, Terri H., Marazita, Mary L., and Murray, Jeffrey C.

Published
2015
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22. Inflammatory Bowel Diseases Before and After 1990

Author

Truta, Brindusa, primary, Begum, Ferdouse, additional, Datta, Lisa Wu, additional, Brant, Steven R., additional, Cho, Judy H., additional, Duerr, Richard H., additional, McGovern, Dermot B.P., additional, Rioux, John R., additional, and Silverberg, Mark S., additional

Published
2023
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23. An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels

Author

Montasser, May E., O’Hare, Elizabeth A., Wang, Xiaochun, Howard, Alicia D., McFarland, Rebecca, Perry, James A., Ryan, Kathleen A., Rice, Kenneth, Jaquish, Cashell E., Shuldiner, Alan R., Miller, Michael, Mitchell, Braxton D., Zaghloul, Norann A., Chang, Yen-Pei C., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette P., Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Debora, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Graham Barr, R., Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russel, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carlson, Sara, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Malia, Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Charles Gu, C., Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Huston, Haley, Hwu, Chii Min, Irvin, Marguerite, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton, Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi Johns, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O’Connell, Jeff, O’Connor, Tim, Heather, Ochs-Balcom, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Pattison, Jessica Tangarone, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Larry, Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Benjamin Shoemaker, M., Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Fei Wang, Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Keoki Williams, L., Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Published
2018
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24. Development of a Blood-based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease

Author

Moll, Matthew, primary, Boueiz, Adel, additional, Ghosh, Auyon J., additional, Saferali, Aabida, additional, Lee, Sool, additional, Xu, Zhonghui, additional, Yun, Jeong H., additional, Hobbs, Brian D., additional, Hersh, Craig P., additional, Sin, Don D., additional, Tal-Singer, Ruth, additional, Silverman, Edwin K., additional, Cho, Michael H., additional, Castaldi, Peter J., additional, Crapo, James D., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Prokopenko, Dmitry, additional, Qiao, Dandi, additional, Sakornsakolpat, Phuwanat, additional, Wan, Emily S., additional, Centeno, Juan Pablo, additional, Charbonnier, Jean-Paul, additional, Coxson, Harvey O., additional, Galban, Craig J., additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Nardelli, Pietro, additional, Newell, John D., additional, Notary, Aleena, additional, Oh, Andrea, additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Vegas Sanchez-Ferrero, Gonzalo, additional, Veitel, Lucas, additional, Washko, George R., additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Pratte, Katherine, additional, Strand, Matt, additional, Kinney, Gregory, additional, Young, Kendra A., additional, Bhatt, Surya P., additional, Bon, Jessica, additional, Diaz, Alejandro A., additional, Murray, Susan, additional, Soler, Xavier, additional, Bowler, Russell P., additional, Kechris, Katerina, additional, and Banaei-Kashani, Farnoush, additional

Published
2022
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25. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A Post Hoc Analysis of the COPDGene and SPIROMICS Cohorts

Author

Iyer, Anand S., primary, Parekh, Trisha M., additional, O’Toole, Jacqueline, additional, Bhatt, Surya P., additional, Eakin, Michelle N., additional, Krishnan, Jerry A., additional, Yohannes, Abebaw M., additional, Woodruff, Prescott G., additional, Cooper, Christopher B., additional, Kanner, Richard E., additional, Hanania, Nicola A., additional, Dransfield, Mark T., additional, Regan, Elizabeth A., additional, Hoth, Karin F., additional, Kim, Victor, additional, Crapo, James D., additional, Silverman, Edwin K., additional, Make, Barry J., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Castaldi, Peter J., additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hayden, Lystra P., additional, Hersh, Craig P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Prokopenko, Dmitry, additional, Qiao, Dandi, additional, Sakornsakolpat, Phuwanat, additional, Wan, Emily S., additional, Won, Sungho, additional, Centeno, Juan Pablo, additional, Charbonnier, Jean-Paul, additional, Coxson, Harvey O., additional, Galban, Craig J., additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Huries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Nardelli, Pietro, additional, Newell, John D., additional, Notary, Aleena, additional, Oh, Andrea, additional, Ross, James C., additional, Estépar, Raul San José, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Sanchez-Ferrero, Gonzalo Vegas, additional, Veitel, Lucas, additional, Washko, George R., additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Pratte, Katherine, additional, Strand, Matt, additional, Kinney, Gregory, additional, Young, Kendra A., additional, Bon, Jessica, additional, Diaz, Alejandro A., additional, Make, Barry, additional, Murray, Susan, additional, Regan, Elizabeth, additional, Soler, Xavier, additional, Bowler, Russell P., additional, Kechris, Katerina, additional, Banaei-Kashani, Farnoush, additional, Curtis, Jeffrey L., additional, Pernicano, Perry G., additional, Hanania, Nicola, additional, Atik, Mustafa, additional, Boriek, Aladin, additional, Guntupalli, Kalpatha, additional, Guy, Elizabeth, additional, Parulekar, Amit, additional, Hersh, Craig, additional, Washko, George, additional, Barr, R. Graham, additional, Austin, John, additional, D’Souza, Belinda, additional, Thomashow, Byron, additional, MacIntyre, Neil, additional, McAdams, H. Page, additional, Wise, Robert, additional, Brown, Robert, additional, Hansel, Nadia N., additional, Horton, Karen, additional, Lambert, Allison, additional, Angeles, Los, additional, Casaburi, Richard, additional, Adami, Alessandra, additional, Budoff, Matthew, additional, Fischer, Hans, additional, Porszasz, Janos, additional, Rossiter, Harry, additional, Stringer, William, additional, Sharafkhaneh, Amir, additional, Lan, Charlie, additional, Wendt, Christine, additional, Bell, Brian, additional, Kunisaki, Ken M., additional, Bowler, Russell, additional, Rosiello, Richard, additional, Pace, David, additional, Criner, Gerard, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D’Alonzo, Gilbert, additional, Desai, Parag, additional, Jacobs, Michael, additional, Kelsen, Steven, additional, Mamary, A. James, additional, Marchetti, Nathaniel, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Steiner, Robert M., additional, Swift, Alex, additional, Swift, Irene, additional, Vega-Sanchez, Maria Elena, additional, Dransfield, Mark, additional, Bailey, William, additional, Iyer, Anand, additional, Nath, Hrudaya, additional, Wells, J. Michael, additional, Conrad, Douglas, additional, Yen, Andrew, additional, Comellas, Alejandro P., additional, Newell, John, additional, Thompson, Brad, additional, Kazerooni, Ella, additional, Labaki, Wassim, additional, Galban, Craig, additional, Vummidi, Dharshan, additional, Billings, Joanne, additional, Begnaud, Abbie, additional, Allen, Tadashi, additional, Sciurba, Frank, additional, Chandra, Divay, additional, Fuhrman, Carl, additional, Weissfeld, Joel, additional, Anzueto, Antonio, additional, Adams, Sandra, additional, Maselli-Caceres, Diego, additional, Ruiz, Mario E., additional, and Singh, Harjinder, additional

Published
2022
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29. Genome-wide association Scan of dental caries in the permanent dentition

Author

Wang Xiaojing, Shaffer John R, Zeng Zhen, Begum Ferdouse, Vieira Alexandre R, Noel Jacqueline, Anjomshoaa Ida, Cuenco Karen T, Lee Myoung-Keun, Beck James, Boerwinkle Eric, Cornelis Marilyn C, Hu Frank B, Crosslin David R, Laurie Cathy C, Nelson Sarah C, Doheny Kimberly F, Pugh Elizabeth W, Polk Deborah E, Weyant Robert J, Crout Richard, McNeil Daniel W, Weeks Daniel E, Feingold Eleanor, and Marazita Mary L

Subjects
Dental caries, Genetics, Genome wide association, Permanent dentition, Genomics, Dentistry, RK1-715
Abstract

Abstract Background Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults. Methods Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries. Results Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens. Conclusions As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.

Published
2012
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30. The St. George’s Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition

Author

Kim, Victor, primary, Zhao, Huaqing, additional, Regan, Elizabeth, additional, Han, MeiLan K., additional, Make, Barry J., additional, Crapo, James D., additional, Jones, Paul W., additional, Curtis, Jeffrey L., additional, Silverman, Edwin K., additional, Criner, Gerard J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Busch, Robert, additional, Castaldi, Peter J., additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hansel, Nadia N., additional, Hardin, Megan E., additional, Hayden, Lystra P., additional, Hersh, Craig P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Qiao, Dandi, additional, Santorico, Stephanie, additional, Wan, Emily S., additional, Won, Sungho, additional, Charbonnier, Jean-Paul, additional, Coxson, Harvey O., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Newell, John D., additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Sieren, Jered, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, Young, Kendra A., additional, Martinez, Carlos H., additional, Pernicano, Perry G., additional, Hanania, Nicola, additional, Alapat, Philip, additional, Atik, Mustafa, additional, Bandi, Venkata, additional, Boriek, Aladin, additional, Guntupalli, Kalpatha, additional, Guy, Elizabeth, additional, Nachiappan, Arun, additional, Parulekar, Amit, additional, Hersh, Craig, additional, Barr, R. Graham, additional, Austin, John, additional, D’Souza, Belinda, additional, Pearson, Gregory D.N., additional, Rozenshtein, Anna, additional, Thomashow, Byron, additional, MacIntyre, Neil, additional, McAdams, H. Page, additional, Washington, Lacey, additional, McEvoy, Charlene, additional, Tashjian, Joseph, additional, Wise, Robert, additional, Brown, Robert, additional, Horton, Karen, additional, Lambert, Allison, additional, Putcha, Nirupama, additional, Casaburi, Richard, additional, Adami, Alessandra, additional, Budoff, Matthew, additional, Fischer, Hans, additional, Porszasz, Janos, additional, Rossiter, Harry, additional, Stringer, William, additional, Sharafkhaneh, Amir, additional, Lan, Charlie, additional, Wendt, Christine, additional, Bell, Brian, additional, Berkowitz, Eugene, additional, Flenaugh, Eric L., additional, Westney, Gloria, additional, Bowler, Russell, additional, Rosiello, Richard, additional, Pace, David, additional, Criner, Gerard, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D’Alonzo, Gilbert, additional, Desai, Parag, additional, Jacobs, Michael, additional, Kelsen, Steven, additional, Kim, Victor, additional, Mamary, A. James, additional, Marchetti, Nathaniel, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Steiner, Robert M., additional, Vega-Sanchez, Maria Elena, additional, Dransfield, Mark, additional, Bailey, William, additional, Bhatt, Surya, additional, Iyer, Anand, additional, Nath, Hrudaya, additional, Oates, Gabriela, additional, Sonavane, Sushil, additional, Wells, J. Michael, additional, Ramsdell, Joe, additional, Friedman, Paul, additional, Soler, Xavier, additional, Yen, Andrew, additional, Comellas, Alejandro P., additional, Newell, John, additional, Thompson, Brad, additional, Kazerooni, Ella, additional, Billings, Joanne, additional, Begnaud, Abbie, additional, Allen, Tadashi, additional, Sciurba, Frank, additional, Bon, Jessica, additional, Chandra, Divay, additional, Fuhrman, Carl, additional, Weissfeld, Joel, additional, Anzueto, Antonio, additional, Adams, Sandra, additional, Maselli-Caceres, Diego, additional, and Ruiz, Mario E., additional

Published
2019
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31. Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease

Author

Fortis, Spyridon, primary, Comellas, Alejandro, additional, Make, Barry J., additional, Hersh, Craig P., additional, Bodduluri, Sandeep, additional, Georgopoulos, Dimitris, additional, Kim, Victor, additional, Criner, Gerard J., additional, Dransfield, Mark T., additional, Bhatt, Surya P., additional, Crapo, James D., additional, Silverman, Edwin K., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Busch, Robert, additional, Castaldi, Peter J., additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hansel, Nadia N., additional, Hardin, Megan E., additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Qiao, Dandi, additional, Santorico, Stephanie, additional, Wan, Emily S., additional, Won, Sungho, additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Newell, John D., additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, Young, Kendra A., additional, Curtis, Jeffrey L., additional, Martinez, Carlos H., additional, Pernicano, Perry G., additional, Hanania, Nicola, additional, Alapat, Philip, additional, Atik, Mustafa, additional, Bandi, Venkata, additional, Boriek, Aladin, additional, Guntupalli, Kalpatha, additional, Guy, Elizabeth, additional, Nachiappan, Arun, additional, Parulekar, Amit, additional, Hersh, Craig, additional, Barr, R. Graham, additional, Austin, John, additional, D’Souza, Belinda, additional, Pearson, Gregory D.N., additional, Rozenshtein, Anna, additional, Thomashow, Byron, additional, MacIntyre, Neil, additional, McAdams, H. Page, additional, Washington, Lacey, additional, McEvoy, Charlene, additional, Tashjian, Joseph, additional, Wise, Robert, additional, Brown, Robert, additional, Horton, Karen, additional, Lambert, Allison, additional, Putcha, Nirupama, additional, Casaburi, Richard, additional, Adami, Alessandra, additional, Budoff, Matthew, additional, Fischer, Hans, additional, Porszasz, Janos, additional, Rossiter, Harry, additional, Stringer, William, additional, Sharafkhaneh, Amir, additional, Lan, Charlie, additional, Wendt, Christine, additional, Bell, Brian, additional, Berkowitz, Eugene, additional, Westney, Gloria, additional, Bowler, Russell, additional, Rosiello, Richard, additional, Pace, David, additional, Criner, Gerard, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D’Alonzo, Gilbert, additional, Desai, Parag, additional, Jacobs, Michael, additional, Kelsen, Steven, additional, Mamary, A. James, additional, Marchetti, Nathaniel, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Steiner, Robert M., additional, Swift, Alex, additional, Swift, Irene, additional, Vega-Sanchez, Maria Elena, additional, Dransfield, Mark, additional, Bailey, William, additional, Bhatt, Surya, additional, Iyer, Anand, additional, Nath, Hrudaya, additional, Wells, J. Michael, additional, Ramsdell, Joe, additional, Friedman, Paul, additional, Soler, Xavier, additional, Yen, Andrew, additional, Comellas, Alejandro P., additional, Newell, John, additional, Thompson, Brad, additional, Kazerooni, Ella, additional, Billings, Joanne, additional, Begnaud, Abbie, additional, Allen, Tadashi, additional, Sciurba, Frank, additional, Bon, Jessica, additional, Chandra, Divay, additional, Fuhrman, Carl, additional, Weissfeld, Joel, additional, Anzueto, Antonio, additional, Adams, Sandra, additional, Maselli-Caceres, Diego, additional, and Ruiz, Mario E., additional

Published
2019
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32. Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution

Author

Boueiz, Adel, primary, Pham, Betty, additional, Chase, Robert, additional, Lamb, Andrew, additional, Lee, Sool, additional, Naing, Zun Zar Chi, additional, Cho, Michael H., additional, Parker, Margaret M., additional, Sakornsakolpat, Phuwanat, additional, Hersh, Craig P., additional, Crapo, James D., additional, Stergachis, Andrew B., additional, Tal-Singer, Ruth, additional, DeMeo, Dawn L., additional, Silverman, Edwin K., additional, Zhou, Xiaobo, additional, Castaldi, Peter J., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Cho, Michael, additional, Boueiz, Adel, additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Qiao, Dandi, additional, Wan, Emily S., additional, Won, Sungho, additional, Prokopenko, Dmitry, additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Newell, John D., additional, Ross, James C., additional, Estepar, Raul San Jose, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, Young, Kendra A., additional, Bhatt, Surya, additional, Bon, Jessica, additional, Make, Barry, additional, Martinez, Carlos, additional, Murray, Susan, additional, Regan, Elizabeth, additional, Soler, Xavier, additional, Bowler, Russell P., additional, Kechris, Katerina, additional, Banaei-Kashani, Farnoush, additional, Ivanov, Y., additional, Kostov, K., additional, Bourbeau, J., additional, Fitzgerald, M., additional, Hernandez, P., additional, Killian, K., additional, Levy, R., additional, Maltais, F., additional, O’Donnell, D., additional, Krepelka, J., additional, Vestbo, J., additional, Wouters, E., additional, Quinn, D., additional, Bakke, P., additional, Kosnik, M., additional, Agusti, A., additional, Sauleda, J., additional, Feschenko, Y., additional, Gavrisyuk, V., additional, Yashina, L., additional, Monogarova, N., additional, Calverley, P., additional, Lomas, D., additional, MacNee, W., additional, Singh, D., additional, Wedzicha, J., additional, Anzueto, A., additional, Braman, S., additional, Casaburi, R., additional, Celli, B., additional, Giessel, G., additional, Gotfried, M., additional, Greenwald, G., additional, Mirage, Rancho, additional, Hanania, N., additional, Mahler, D., additional, Make, B., additional, Rennard, S., additional, Rochester, C., additional, Scanlon, P., additional, Schuller, D., additional, Sciurba, F., additional, Sharafkhaneh, A., additional, Siler, T., additional, Silverman, E., additional, Wanner, A., additional, Wise, R., additional, ZuWallack, R., additional, Coxson, H., additional, Crim, C., additional, Edwards, L., additional, Tal-Singer, R., additional, Yates, J., additional, Miller, B., additional, Bakke, Per, additional, and Gulsvik, Amund, additional

Published
2019
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33. Mucus plugging on computed tomography and chronic bronchitis in chronic obstructive pulmonary disease.

Author

Kim, Victor, Dolliver, Wojciech R., Nath, Hrudaya P., Grumley, Scott A., Terry, Nina, Ahmed, Asmaa, Yen, Andrew, Jacobs, Kathleen, Kligerman, Seth, Diaz, Alejandro A., the COPDGene Investigators, Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J., Cho, Michael, and DeMeo, Dawn L.

Subjects
OBSTRUCTIVE lung diseases, COMPUTED tomography, CHRONIC bronchitis, MUCUS
Abstract

Chronic bronchitis (CB) is associated with more dyspnea, increased respiratory exacerbations, reduced exercise capacity, and mortality [[1]]. Mucus plugging (MP) on CT scan has been associated with decreased lung function, worse health-related quality of life, and amount of emphysema in Chronic Obstructive Pulmonary Disease (COPD) [[3]]. MP+ was associated with an OR of 1.21 and 1.38 for classic CB and SGRQ CB, respectively when adjusting for demographics, lung function, smoking, and CT measures of emphysema and airway wall thickness. In the MP >= 4 group, the differences were more significant with 57.7% and 41.4% of the subjects having SGRQ CB and classic CB, respectively, compared to 27.6% and 23.8% of the MP < 4 group. [Extracted from the article]

Published
2021
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34. Vitamin D deficiency is associated with respiratory symptoms and airway wall thickening in smokers with and without COPD: a prospective cohort study.

Author

Ghosh, Auyon J., Moll, Matthew, Hayden, Lystra P., Bon, Jessica, Regan, Elizabeth, Hersh, Craig P., the COPDGene Investigators, Crapo, James D., Silverman, Edwin K., Make, Barry J., Regan, Elizabeth A., Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J., Cho, Michael, DeMeo, Dawn L., Boueiz, Adel R., Foreman, Marilyn G., Halper-Stromberg, Eitan, and Hetmanski, Jacqueline

Subjects
VITAMIN D deficiency, OBSTRUCTIVE lung diseases, ALPHA 1-antitrypsin deficiency, LONGITUDINAL method, VITAMIN D, EXERCISE tolerance
Abstract

Background: Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial. In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored. Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics. We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes.Methods: Current and former smokers between ages 45-80 were enrolled the COPDGene Study. Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans. A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D). Vitamin D deficiency was defined as serum concentration less than 20 ng/mL. Longitudinal follow up was conducted via a web-based or telephone questionnaire.Results: Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency. Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV1, and having COPD. Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations. Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans.Conclusion: Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans. Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes. [ABSTRACT FROM AUTHOR]

Published
2020
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35. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Author

Wan, Emily S., primary, Fortis, Spyridon, additional, Regan, Elizabeth A., additional, Hokanson, John, additional, Han, MeiLan K., additional, Casaburi, Richard, additional, Make, Barry J., additional, Crapo, James D., additional, DeMeo, Dawn L., additional, Silverman, Edwin K., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Castaldi, Peter J., additional, Cho, Michael, additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hayden, Lystra P., additional, Hersh, Craig P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Qiao, Dandi, additional, Wan, Emily S., additional, Won, Sungho, additional, Sakornsakolpat, Phuwanat, additional, Prokopenko, Dmitry, additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Newell, John D., additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, Young, Kendra A., additional, Bhatt, Surya, additional, Bon, Jessica, additional, Make, Barry, additional, Martinez, Carlos, additional, Murray, Susan, additional, Regan, Elizabeth, additional, Soler, Xavier, additional, Bowler, Russell P., additional, Kechris, Katerina, additional, Banaei-Kashani, Farnoush, additional, Curtis, Jeffrey L., additional, Martinez, Carlos H., additional, Pernicano, Perry G., additional, Hanania, Nicola, additional, Alapat, Philip, additional, Atik, Mustafa, additional, Bandi, Venkata, additional, Boriek, Aladin, additional, Guntupalli, Kalpatha, additional, Guy, Elizabeth, additional, Nachiappan, Arun, additional, Parulekar, Amit, additional, Hersh, Craig, additional, Barr, R. Graham, additional, Austin, John, additional, D’Souza, Belinda, additional, Pearson, Gregory D. N., additional, Rozenshtein, Anna, additional, Thomashow, Byron, additional, MacIntyre, Neil, additional, McAdams, H. Page, additional, Washington, Lacey, additional, McEvoy, Charlene, additional, Tashjian, Joseph, additional, Wise, Robert, additional, Brown, Robert, additional, Hansel, Nadia N., additional, Horton, Karen, additional, Lambert, Allison, additional, Putcha, Nirupama, additional, Adami, Alessandra, additional, Budoff, Matthew, additional, Fischer, Hans, additional, Porszasz, Janos, additional, Rossiter, Harry, additional, Stringer, William, additional, Sharafkhaneh, Amir, additional, Lan, Charlie, additional, Wendt, Christine, additional, Bell, Brian, additional, Berkowitz, Eugene, additional, Westney, Gloria, additional, Bowler, Russell, additional, Rosiello, Richard, additional, Pace, David, additional, Criner, Gerard, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D’Alonzo, Gilbert, additional, Desai, Parag, additional, Jacobs, Michael, additional, Kelsen, Steven, additional, Kim, Victor, additional, Mamary, A. James, additional, Marchetti, Nathaniel, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Steiner, Robert M., additional, Swift, Alex, additional, Swift, Irene, additional, Vega-Sanchez, Maria Elena, additional, Dransfield, Mark, additional, Bailey, William, additional, Iyer, Anand, additional, Nath, Hrudaya, additional, Wells, J. Michael, additional, Ramsdell, Joe, additional, Friedman, Paul, additional, Yen, Andrew, additional, Comellas, Alejandro P., additional, Hoth, Karin F., additional, Newell, John, additional, Thompson, Brad, additional, Kazerooni, Ella, additional, Billings, Joanne, additional, Begnaud, Abbie, additional, Allen, Tadashi, additional, Sciurba, Frank, additional, Chandra, Divay, additional, Fuhrman, Carl, additional, Weissfeld, Joel, additional, Anzueto, Antonio, additional, Adams, Sandra, additional, Maselli-Caceres, Diego, additional, and Ruiz, Mario E., additional

Published
2018
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36. Inferring disease risk genes from sequencing data in multiplex pedigrees through sharing of rare variants

Author

Bureau, Alexandre, primary, Begum, Ferdouse, additional, Taub, Margaret A., additional, Hetmanski, Jacqueline B., additional, Parker, Margaret M., additional, Albacha-Hejazi, Hasan, additional, Scott, Alan F., additional, Murray, Jeffrey C., additional, Marazita, Mary L., additional, Bailey-Wilson, Joan E., additional, Beaty, Terri H., additional, and Ruczinski, Ingo, additional

Published
2018
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37. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

Author

Ekström, Magnus, primary, Bornefalk-Hermansson, Anna, additional, Wysham, Nicholas, additional, Currow, David C., additional, MacIntyre, Neil, additional, Crapo, James D., additional, Silverman, Edwin K., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Busch, Robert, additional, Castaldi, Peter J., additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Boueiz, Adel R., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hansel, Nadia N., additional, Hardin, Megan E., additional, Hayden, Lystra P., additional, Hersh, Craig P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Qiao, Dandi, additional, Santorico, Stephanie, additional, Wan, Emily S., additional, Won, Sungho, additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Lynch, David A., additional, Newell, John D., additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Everett, Douglas, additional, Crooks, Jim, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, Young, Kendra A., additional, Curtis, Jeffrey L., additional, Martinez, Carlos H., additional, Pernicano, Perry G., additional, Hanania, Nicola, additional, Alapat, Philip, additional, Atik, Mustafa, additional, Bandi, Venkata, additional, Boriek, Aladin, additional, Guntupalli, Kalpatha, additional, Guy, Elizabeth, additional, Nachiappan, Arun, additional, Parulekar, Amit, additional, Hersh, Craig, additional, Barr, R. Graham, additional, Austin, John, additional, D’Souza, Belinda, additional, Pearson, Gregory D. N., additional, Rozenshtein, Anna, additional, Thomashow, Byron, additional, McAdams, H. Page, additional, Washington, Lacey, additional, McEvoy, Charlene, additional, Tashjian, Joseph, additional, Wise, Robert, additional, Brown, Robert, additional, Horton, Karen, additional, Lambert, Allison, additional, Putcha, Nirupama, additional, Casaburi, Richard, additional, Adami, Alessandra, additional, Budoff, Matthew, additional, Fischer, Hans, additional, Porszasz, Janos, additional, Rossiter, Harry, additional, Stringer, William, additional, Sharafkhaneh, Amir, additional, Lan, Charlie, additional, Wendt, Christine, additional, Bell, Brian, additional, Berkowitz, Eugene, additional, Westney, Gloria, additional, Bowler, Russell, additional, Rosiello, Richard, additional, Pace, David, additional, Criner, Gerard, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D’Alonzo, Gilbert, additional, Desai, Parag, additional, Pharm.D, Michael Jacobs, additional, Kelsen, Steven, additional, Kim, Victor, additional, Mamary, A. James, additional, Marchetti, Nathaniel, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Steiner, Robert M., additional, Swift, Alex, additional, Swift, Irene, additional, Vega-Sanchez, Maria Elena, additional, Dransfield, Mark, additional, Bailey, William, additional, Bhatt, Surya, additional, Iyer, Anand, additional, Nath, Hrudaya, additional, Wells, J. Michael, additional, Ramsdell, Joe, additional, Friedman, Paul, additional, Soler, Xavier, additional, Yen, Andrew, additional, Comellas, Alejandro P., additional, Newell, John, additional, Thompson, Brad, additional, Kazerooni, Ella, additional, Billings, Joanne, additional, Begnaud, Abbie, additional, Allen, Tadashi, additional, Sciurba, Frank, additional, Bon, Jessica, additional, Chandra, Divay, additional, Fuhrman, Carl, additional, Weissfeld, Joel, additional, Anzueto, Antonio, additional, Adams, Sandra, additional, Maselli-Caceres, Diego, additional, and Ruiz, Mario E., additional

Published
2018
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38. Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios

Author

Xiao, Yanzi, Taub, Margaret A., Ruczinski, Ingo, Begum, Ferdouse, Hetmanski, Jacqueline B., Schwender, Holger, Leslie, Elizabeth J., Koboldt, Daniel C., Murray, Jeffrey C., Marazita, Mary L., and Beaty, Terri H.

Subjects
Male, Parents, Cleft Lip, Epistasis, Genetic, Polymorphism, Single Nucleotide, Article, White People, Cleft Palate, Asian People, Risk Factors, Ethnicity, Humans, Female, Genome-Wide Association Study
Abstract

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, affecting 1 in 700 live births. This malformation has a complex etiology where multiple genes and several environmental factors influence risk. At least a dozen different genes have been confirmed to be associated with risk of NSCL/P in previous studies. However, all the known genetic risk factors cannot fully explain the observed heritability of NSCL/P, and several authors have suggested gene-gene (G×G) interaction may be important in the etiology of this complex and heterogeneous malformation. We tested for G×G interactions using common SNPs derived from targeted sequencing in 13 regions identified by previous studies spanning 6.3 MB of the genome in a study of 1,498 NSCL/P case-parent trios. We used the R-package trio to assess interactions between polymorphic markers in different genes, using a 1 degree of freedom (1df) test for screening, and a 4 degree of freedom (4df) test to assess statistical significance of epistatic interactions. To adjust for multiple comparisons, we performed permutation tests. The most significant interaction was observed between rs6029315 in MAFB and rs6681355 in IRF6 (4df p=3.8×10−8) in case-parent trios of European ancestry, which remained significant after correcting for multiple comparisons. However, no significant interaction was detected in trios of Asian ancestry.

Published
2016

39. Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline

Author

Hayden, Lystra P., primary, Hardin, Megan E., additional, Qiu, Weiliang, additional, Lynch, David A., additional, Strand, Matthew J., additional, van Beek, Edwin J., additional, Crapo, James D., additional, Silverman, Edwin K., additional, Hersh, Craig P., additional, Make, Barry J., additional, Regan, Elizabeth A., additional, Beaty, Terri, additional, Begum, Ferdouse, additional, Boueiz, Adel R., additional, Busch, Robert, additional, Castaldi, Peter J., additional, Cho, Michael, additional, DeMeo, Dawn L., additional, Foreman, Marilyn G., additional, Halper-Stromberg, Eitan, additional, Hansel, Nadia N., additional, Hayden, Lystra P., additional, Hetmanski, Jacqueline, additional, Hobbs, Brian D., additional, Hokanson, John E., additional, Laird, Nan, additional, Lange, Christoph, additional, Lutz, Sharon M., additional, McDonald, Merry-Lynn, additional, Parker, Margaret M., additional, Qiao, Dandi, additional, Santorico, Stephanie, additional, Wan, Emily S., additional, Al Qaisi, Mustafa, additional, Coxson, Harvey O., additional, Gray, Teresa, additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Kluiber, Alex, additional, Newell, John D., additional, Ross, James C., additional, Estepar, Raul San Jose, additional, Schroeder, Joyce, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Van Beek, Edwin, additional, van Ginneken, Bram, additional, van Rikxoort, Eva, additional, Washko, George, additional, Wilson, Carla G., additional, Jensen, Robert, additional, Crooks, Jim, additional, Everett, Douglas, additional, Moore, Camille, additional, Strand, Matt, additional, Hughes, John, additional, Kinney, Gregory, additional, Pratte, Katherine, additional, and Young, Kendra A., additional

Published
2018
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40. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Author

Adams, Sandra, Swift, Irene, El-Bouiez, Adel, Weissfeld, Joel, Guy, Elizabeth, Mann, Tanya, Qiao, Dandi, Maselli-Caceres, Diego, Hokanson, John E., McEvoy, Charlene, LaVange, Lisa M., O’Neal, Wanda K., Ruiz, Mario E., Kanner, Richard E., Ross, James C, Jacobson, Francine, Tschirren, Juerg, Fuhrman, Carl, Thompson, Brad, Kelsen, Steven, Chen, Ting-Huei, Humphries, Stephen, Bell, Brian, Al Qaisi, Mustafa, Jacobs, Michael, San Jose Estepar, Raul, Bowler, Russell, Dransfield, Mark, Alexis, Neil E., Cho, Michael, Newell, John, Crapo, James, Wilson, Carla, Curtis, Jeffrey L., Tashjian, Joseph, Rosiello, Richard, Rossiter, Harry, Swift, Alex, Washko, George, Peters, Stephen P., Fischer, Hans, Hardin, Megan, Stinson, Douglas, Adami, Alessandra, Lazarus, Stephen C., Cooper, Christopher B., Duca, Lindsey, Berkowitz, Eugene, Han, MeiLan K., Busch, Robert, Hoffman, Eric A., Anzueto, Antonio, Ciccolella, David, Han, MeiLan, Hansel, Nadia, Washington, Lacey, Castaldi, Peter, Desai, Parag, Wise, Robert A., Begum, Ferdouse, Parulekar, Amit, Sun, Wei, Cho, Michael H., Budoff, Matthew, Beaty, Terri, Strand, Matt, Kluiber, Alex, Judy, Philip F, Bailey, William, Soler, Xavier, Dransfield, Mark T., Regan, Elizabeth, Carretta, Elizabeth E., Parker, Margaret, Lynch, David A., Bhatt, Surya, Friedman, Paul, Everett, Douglas, Hawkins, Gregory A., Kechris, Katerina, Sieren, Jered, Lutz, Sharon, Sciurba, Frank, Wise, Robert, Hersh, Craig P., Schroeder, Joyce, Chandra, Divay, Kazerooni, Ella A, Wendt, Christine, Won, Sungho, Nachiappan, Arun, Stoel, Berend C, Bandi, Venkata, Hanania, Nicola A., Dass, Chandra, Horton, Karen, Wan, Emily, James Mamary, Paine, Robert, Pace, David, Freeman, Christine M., Brown, Robert, Newell, John D., McDonald, Merry-Lynn, Boucher, Richard C., Alapat, Philip, Pratte, Katherine, Bon, Jessica, Vega-Sanchez, Maria Elena, Steiner, Robert M., Austin, John, Martinez, Carlos H., Nath, Hrudaya, Allen, Tadashi, Yang, Jenny, Billings, Joanne, Kleerup, Eric C., van Ginneken, Bram, Lan, Charlie, D'Souza, Belinda, Atik, Mustafa, Hobbs, Brian, Michael Wells, Woodruff, Prescott G., Pearson, Gregory D.N., Comellas, Alejandro, Faino, Anna, Halper-Stromberg, Eitan, Laird, Nan, Sharafkhaneh, Amir, Drummond, M. Bradley, Thomashow, Byron, Comellas, Alejandro P., Foreman, Marilyn, Hersh, Craig, D'Alonzo, Gilbert, Criner, Gerard, Cornellas, Alejandro, Meyers, Deborah A., Jensen, Robert, Couper, David J., Silverman, Edwin K., McAdams, H. Page, Kazerooni, Ella, Jacobson, Francine L, Martinez, Carlos, Casaburi, Richard, Silverman, Edwin, Kim, Victor, Shenoy, Kartik, Yen, Andrew, Putcha, Nirupama, Doerschuk, Claire M., Demeo, Dawn, Gray, Teresa, MacIntyre, Neil, Crapo, James D., Lynch, David, Bleecker, Eugene R., Satti, Aditi, Barr, R. Graham, Gouskova, Natalia A., Boriek, Aladin, Oelsner, Elizabeth C., Tashkin, Donald P., Crystal, Ronald G., Wilson, Carla G, Kaner, Robert J., Jacobson, Sean, Regan, Elizabeth A., De, Dawn, Santorico, Stephanie, Hastie, Annette T., Van Beek, Edwin, Kinney, Gregory, Rennard, Stephen I., Scholand, Mary Beth, Martinez, Fernando J., Hokanson, John, Coxson, Harvey O., Marchetti, Nathaniel, Ramsdell, Joe, Quibrera, Pedro Miguel, Lange, Christoph, Pernicano, Perry G., van Rikxoort, Eva, Young, Kendra, Anderson, Wayne, Hansel, Nadia N., Wells, J. Michael, Hetmanski, Jacqueline, Criner, Gerard J., Porszasz, Janos, Rozenshtein, Anna, Christenson, Stephanie A., Krishnan, Jerry A., Westney, Gloria, Make, Barry, Guntupalli, Kalpatha, Basta, Patricia V., and Cordova, Francis

Abstract

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

Published
2016
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41. Analysis of sequence data to identify potential risk variants for oral clefts in multiplex families

Author

Holzinger, Emily R., primary, Li, Qing, additional, Parker, Margaret M., additional, Hetmanski, Jacqueline B., additional, Marazita, Mary L., additional, Mangold, Elisabeth, additional, Ludwig, Kerstin U., additional, Taub, Margaret A., additional, Begum, Ferdouse, additional, Murray, Jeffrey C., additional, Albacha-Hejazi, Hasan, additional, Alqosayer, Khalid, additional, Al-Souki, Giath, additional, Albasha Hejazi, Abdullatiff, additional, Scott, Alan F., additional, Beaty, Terri H., additional, and Bailey-Wilson, Joan E., additional

Published
2017
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42. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

Author

Busch, Robert, primary, Hobbs, Brian D., additional, Zhou, Jin, additional, Castaldi, Peter J., additional, McGeachie, Michael J., additional, Hardin, Megan E., additional, Hawrylkiewicz, Iwona, additional, Sliwinski, Pawel, additional, Yim, Jae-Joon, additional, Kim, Woo Jin, additional, Kim, Deog K., additional, Agusti, Alvar, additional, Make, Barry J., additional, Crapo, James D., additional, Calverley, Peter M., additional, Donner, Claudio F., additional, Lomas, David A., additional, Wouters, Emiel F., additional, Vestbo, Jørgen, additional, Tal-Singer, Ruth, additional, Bakke, Per, additional, Gulsvik, Amund, additional, Litonjua, Augusto A., additional, Sparrow, David, additional, Paré, Peter D., additional, Levy, Robert D., additional, Rennard, Stephen I., additional, Beaty, Terri H., additional, Hokanson, John, additional, Silverman, Edwin K., additional, Cho, Michael H., additional, Crapo, James, additional, Silverman, Edwin, additional, Make, Barry, additional, Regan, Elizabeth, additional, Beaty, Terri, additional, Laird, Nan, additional, Lange, Christoph, additional, Cho, Michael, additional, Santorico, Stephanie, additional, DeMeo, Dawn, additional, Hansel, Nadia, additional, Hersh, Craig, additional, Castaldi, Peter, additional, McDonald, Merry-Lynn, additional, Wan, Emily, additional, Hardin, Megan, additional, Hetmanski, Jacqueline, additional, Parker, Margaret, additional, Foreman, Marilyn, additional, Hobbs, Brian, additional, Busch, Robert, additional, El-Bouiez, Adel, additional, Qiao, Dandi, additional, Halper-Stromberg, Eitan, additional, Begum, Ferdouse, additional, Won, Sungho, additional, Lutz, Sharon, additional, Lynch, David A., additional, Coxson, Harvey O., additional, Han, MeiLan K., additional, Hoffman, Eric A., additional, Humphries, Stephen, additional, Jacobson, Francine L., additional, Judy, Philip F., additional, Kazerooni, Ella A., additional, Newell, John D., additional, Ross, James C., additional, San Jose Estepar, Raul, additional, Stoel, Berend C., additional, Tschirren, Juerg, additional, Rikxoort, Eva van, additional, Ginneken, Bram van, additional, Washko, George, additional, Wilson, Carla G., additional, Al Qaisi, Mustafa, additional, Gray, Teresa, additional, Kluiber, Alex, additional, Mann, Tanya, additional, Sieren, Jered, additional, Stinson, Douglas, additional, Schroeder, Joyce, additional, Van Beek, Edwin, additional, Jensen, Robert, additional, Everett, Douglas, additional, Faino, Anna, additional, Strand, Matt, additional, Wilson, Carla, additional, Hokanson, John E., additional, Kinney, Gregory, additional, Young, Kendra, additional, Pratte, Katherine, additional, Duca, Lindsey, additional, Curtis, Jeffrey L., additional, Martinez, Carlos H., additional, Pernicano, Perry G., additional, Hanania, Nicola, additional, Alapat, Philip, additional, Bandi, Venkata, additional, Atik, Mustafa, additional, Boriek, Aladin, additional, Guntupalli, Kalpatha, additional, Guy, Elizabeth, additional, Parulekar, Amit, additional, Nachiappan, Arun, additional, Jacobson, Francine, additional, Barr, R. Graham, additional, Thomashow, Byron, additional, Austin, John, additional, D'Souza, Belinda, additional, Pearson, Gregory D. N., additional, Rozenshtein, Anna, additional, MacIntyre, Neil, additional, Washington, Lacey, additional, McAdams, H. Page, additional, McEvoy, Charlene, additional, Tashjian, Joseph, additional, Wise, Robert, additional, Brown, Robert, additional, Horton, Karen, additional, Putcha, Nirupama, additional, Casaburi, Richard, additional, Adami, Alessandra, additional, Porszasz, Janos, additional, Fischer, Hans, additional, Budoff, Matthew, additional, Rossiter, Harry, additional, Sharafkhaneh, Amir, additional, Lan, Charlie, additional, Wendt, Christine, additional, Bell, Brian, additional, Westney, Gloria, additional, Berkowitz, Eugene, additional, Bowler, Russell, additional, Lynch, David, additional, Rosiello, Richard, additional, Pace, David, additional, Criner, Gerard, additional, Ciccolella, David, additional, Cordova, Francis, additional, Dass, Chandra, additional, D'Alonzo, Gilbert, additional, Desai, Parag, additional, Jacobs, Michael, additional, Kelsen, Steven, additional, Kim, Victor, additional, Mamary, A. James, additional, Marchetti, Nathaniel, additional, Satti, Aditi, additional, Shenoy, Kartik, additional, Steiner, Robert M., additional, Swift, Alex, additional, Swift, Irene, additional, Vega-Sanchez, Maria Elena, additional, Dransfield, Mark, additional, Bailey, William, additional, Wells, J. Michael, additional, Bhatt, Surya, additional, Nath, Hrudaya, additional, Ramsdell, Joe, additional, Friedman, Paul, additional, Soler, Xavier, additional, Yen, Andrew, additional, Comellas, Alejandro, additional, Newell, John, additional, Thompson, Brad, additional, Han, MeiLan, additional, Kazerooni, Ella, additional, Martinez, Carlos, additional, Billings, Joanne, additional, Allen, Tadashi, additional, Sciurba, Frank, additional, Chandra, Divay, additional, Weissfeld, Joel, additional, Fuhrman, Carl, additional, Bon, Jessica, additional, Anzueto, Antonio, additional, Adams, Sandra, additional, Maselli-Caceres, Diego, additional, Ruiz, Mario E., additional, Sauleda, Jaume, additional, Calverley, Peter M. A., additional, Rennard, Stephen, additional, Ivanov, Y., additional, Kostov, K., additional, Bourbeau, J., additional, Fitzgerald, M., additional, Hernandez, P., additional, Killian, K., additional, Levy, R., additional, Maltais, F., additional, O'Donnell, D., additional, Krepelka, J., additional, Vestbo, J., additional, Wouters, E., additional, Quinn, D., additional, Bakke, P., additional, Kosnik, M., additional, Agusti, A., additional, Sauleda, J., additional, Feschenko, Y., additional, Gavrisyuk, V., additional, Yashina, L., additional, Monogarova, N., additional, Calverley, P., additional, Lomas, D., additional, MacNee, W., additional, Singh, D., additional, Wedzicha, J., additional, Anzueto, A., additional, Braman, S., additional, Casaburi, R., additional, Celli, B., additional, Giessel, G., additional, Gotfried, M., additional, Greenwald, G., additional, Hanania, N., additional, Mahler, D., additional, Make, B., additional, Rennard, S., additional, Rochester, C., additional, Scanlon, P., additional, Schuller, D., additional, Sciurba, F., additional, Sharafkhaneh, A., additional, Siler, T., additional, Silverman, E., additional, Wanner, A., additional, Wise, R., additional, ZuWallack, R., additional, Coxson, H., additional, Crim, C., additional, Edwards, L., additional, Tal Singer, R., additional, Yates, J., additional, Miller, B., additional, Tal-Singer, R., additional, Benditt, J., additional, Criner, G., additional, DeCamp, M., additional, Diaz, P., additional, Ginsburg, M., additional, Kaiser, L., additional, Katz, M., additional, Krasna, M., additional, MacIntyre, N., additional, McKenna, R., additional, Martinez, F., additional, Mosenifar, Z., additional, Reilly, J., additional, Ries, A., additional, and Utz, J., additional

Published
2017
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44. REGIONALLY SMOOTHED META-ANALYSIS METHODS FOR GWAS DATASETS

Author

Begum, Ferdouse, Sharker, Monir H., Sherman, Stephanie L., Tseng, George C., and Feingold, Eleanor

Subjects
Male, Genotype, Meta-Analysis as Topic, Humans, Computer Simulation, Genetic Predisposition to Disease, Environmental Exposure, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Genome-Wide Association Study
Abstract

Genome-wide association studies are proven tools for finding disease genes, but it is often necessary to combine many cohorts into a meta-analysis to detect statistically significant genetic effects. Often the component studies are performed by different investigators on different populations, using different chips with minimal SNPs overlap. In some cases, raw data are not available for imputation so that only the genotyped single nucleotide polymorphisms (SNPs) results can be used in meta-analysis. Even when SNP sets are comparable, different cohorts may have peak association signals at different SNPs within the same gene due to population differences in linkage disequilibrium or environmental interactions. We hypothesize that the power to detect statistical signals in these situations will improve by using a method that simultaneously meta-analyzes and smooths the signal over nearby markers. In this study, we propose regionally smoothed meta-analysis methods and compare their performance on real and simulated data.

Published
2015

45. Identifying a deletion affecting total lung capacity among subjects in the COPDGene study cohort

Author

Begum, Ferdouse, Ruczinski, Ingo, Li, Shengchao, Silverman, Edwin K., Cho, Michael H., Lynch, David A., Curran-Everett, Douglas, Crapo, James, Scharpf, Robert B., Parker, Margaret M., Hetmanski, Jacqueline B., and Beatyon behalf of the COPDGene investigators, Terri H.

Subjects
Male, DNA Copy Number Variations, Smoking, Total Lung Capacity, Middle Aged, Article, Markov Chains, White People, respiratory tract diseases, Black or African American, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Chromosomes, Human, Pair 5, Humans, Female, Genetic Predisposition to Disease, Chromosome Deletion, Biomarkers, Aged, Genome-Wide Association Study
Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive disease with both environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified multiple genomic regions influencing risk of COPD. To thoroughly investigate the genetic etiology of COPD, however, it is also important to explore the role of copy number variants (CNVs) because the presence of structural variants can alter gene expression and can be causal for some diseases. Here, we investigated effects of polymorphic CNVs on quantitative measures of pulmonary function and chest computed tomography (CT) phenotypes among subjects enrolled in COPDGene, a multisite study. COPDGene subjects consist of roughly one-third African American (AA) and two-thirds non-Hispanic white adult smokers (with or without COPD). We estimated CNVs using PennCNV on 9,076 COPDGene subjects using Illumina's Omni-Express genome-wide marker array. We tested for association between polymorphic CNV components (defined as disjoint intervals of copy number regions) for several quantitative phenotypes associated with COPD within each racial group. Among the AAs, we identified a polymorphic CNV on chromosome 5q35.2 located between two genes (FAM153B and SIMK1, but also harboring several pseudo-genes) giving genome-wide significance in tests of association with total lung capacity (TLCCT ) as measured by chest CT scans. This is the first study of genome-wide association tests of polymorphic CNVs and TLCCT . Although the ARIC cohort did not have the phenotype of TLCCT , we found similar counts of CNV deletions and amplifications among AA and European subjects in this second cohort.

Published
2015

46. Common and Rare Variants Genetic Association Analysis of Cigarettes per Day Among Ever-Smokers in Chronic Obstructive Pulmonary Disease Cases and Controls.

Author

Lutz, Sharon M, Frederiksen, Brittni, Begum, Ferdouse, McDonald, Merry-Lynn N, Cho, Michael H, Hobbs, Brian D, Parker, Margaret M, DeMeo, Dawn L, Hersh, Craig P, Ehringer, Marissa A, Young, Kendra, Jiang, Lai, Foreman, Marilyn G, Kinney, Greg L, Make, Barry J, Lomas, David A, Bakke, Per, Gulsvik, Amund, Crapo, James D, and Silverman, Edwin K

Subjects
OBSTRUCTIVE lung diseases, CHROMOSOME polymorphism, SINGLE nucleotide polymorphisms, CIGARETTES, SMOKING, COMPARATIVE studies, DISEASE susceptibility, ETHNIC groups, GENETIC polymorphisms, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, OXIDOREDUCTASES, PROGNOSIS, PROTEINS, RESEARCH, RESEARCH funding, GENETIC markers, EVALUATION research, DISEASE prevalence, CASE-control method, SEQUENCE analysis
Abstract

Introduction: Cigarette smoking is a major environmental risk factor for many diseases, including chronic obstructive pulmonary disease (COPD). There are shared genetic influences on cigarette smoking and COPD. Genetic risk factors for cigarette smoking in cohorts enriched for COPD are largely unknown.Methods: We performed genome-wide association analyses for average cigarettes per day (CPD) across the Genetic Epidemiology of COPD (COPDGene) non-Hispanic white (NHW) (n = 6659) and African American (AA) (n = 3260), GenKOLS (the Genetics of Chronic Obstructive Lung Disease) (n = 1671), and ECLIPSE (the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) (n = 1942) cohorts. In addition, we performed exome array association analyses across the COPDGene NHW and AA cohorts. We considered analyses across the entire cohort and stratified by COPD case-control status.Results: We identified genome-wide significant associations for CPD on chromosome 15q25 across all cohorts (lowest p = 1.78 × 10-15), except in the COPDGene AA cohort alone. Previously reported associations on chromosome 19 had suggestive and directionally consistent associations (RAB4, p = 1.95 × 10-6; CYP2A7, p = 7.50 × 10-5; CYP2B6, p = 4.04 × 10-4). When we stratified by COPD case-control status, single nucleotide polymorphisms on chromosome 15q25 were nominally associated with both NHW COPD cases (β = 0.11, p = 5.58 × 10-4) and controls (β = 0.12, p = 3.86 × 10-5) For the gene-based exome array association analysis of rare variants, there were no exome-wide significant associations. For these previously replicated associations, the most significant results were among COPDGene NHW subjects for CYP2A7 (p = 5.2 × 10-4).Conclusions: In a large genome-wide association study of both common variants and a gene-based association of rare coding variants in ever-smokers, we found genome-wide significant associations on chromosome 15q25 with CPD for common variants, but not for rare coding variants. These results were directionally consistent among COPD cases and controls.Implications: We examined both common and rare coding variants associated with CPD in a large population of heavy smokers with and without COPD of NHW and AA descent. We replicated genome-wide significant associations on chromosome 15q25 with CPD for common variants among NHW subjects, but not for rare variants. We demonstrated for the first time that common variants on chromosome 15q25 associated with CPD are similar among COPD cases and controls. Previously reported associations on chromosome 19 showed suggestive and directionally consistent associations among common variants (RAB4, CYP2A7, and CYP2B6) and for rare variants (CYP2A7) among COPDGene NHW subjects. Although the genetic effect sizes for these single nucleotide polymorphisms on chromosome 15q25 are modest, we show that this creates a substantial smoking burden over the lifetime of a smoker. [ABSTRACT FROM AUTHOR]

Published
2019
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49. Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among African American Subjects in the COPDGene Study

Author

Begum, Ferdouse, primary, Ruczinski, Ingo, additional, Hokanson, John E., additional, Lutz, Sharon M., additional, Parker, Margaret M., additional, Cho, Michael H., additional, Hetmanski, Jacqueline B., additional, Scharpf, Robert B., additional, Crapo, James D., additional, Silverman, Edwin K., additional, and Beaty, Terri H., additional

Published
2016
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