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1,208 results on '"O'Connor, George T"'

1. Clinical and molecular analysis of longitudinal rhinitis phenotypes in an urban birth cohort

Author

Ramratnam, Sima K., Johnson, Molly, Visness, Cynthia M., Calatroni, Agustin, Altman, Mathew C., Janczyk, Tomasz, McCauley, Kathryn E., Schachtschneider, Claire, Fujimura, Kei E., Fadrosh, Douglas W., Lynch, Susan V., Bacharier, Leonard B., O'Connor, George T., Sandel, Megan T., Kattan, Meyer, Wood, Robert A., Gergen, Peter J., Jackson, Daniel J., Togias, Alkis, and Gern, James E.

Published
2025
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2. Dysregulation of airway and systemic interferon responses promotes asthma exacerbations in urban children

Author

Gaberino, Courtney L., Altman, Matthew C., Gill, Michelle A., Bacharier, Leonard B., Gruchalla, Rebecca S., O’Connor, George T., Kumar, Rajesh, Khurana Hershey, Gurjit K., Kattan, Meyer, Liu, Andrew H., Teach, Stephen J., Zoratti, Edward M., Becker, Patrice M., Togias, Alkis, Visness, Cynthia, Gern, James E., Busse, William W., and Jackson, Daniel J.

Published
2025
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3. Rhinoconjunctivitis symptoms in children and adolescents with asthma: Longitudinal clustering analysis

Author

Togias, Alkis, Gergen, Peter J., Liu, Andrew H., Kim, Haejin, Wood, Robert A., O’Connor, George T., Makhija, Melanie, Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Lamm, Carin, Bacharier, Leonard B., Patel, Shilpa J., Gern, James E., Jackson, Daniel J., Visness, Cynthia M., Calatroni, Agustin, and Busse, William W.

Published
2025
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4. Caregiver worry about COVID-19 as a predictor of social mitigation behaviours and SARS-CoV-2 infection in a 12-city U.S. surveillance study of households with children

Author

Brunwasser, Steven M., Gebretsadik, Tebeb, Satish, Anisha, Cole, Jennifer C., Dupont, William D., Joseph, Christine, Bendixsen, Casper G., Calatroni, Agustin, Arbes, Samuel J., Jr, Fulkerson, Patricia C., Sanders, Joshua, Bacharier, Leonard B., Camargo, Jr, Carlos A., Johnson, Christine Cole, Furuta, Glenn T., Gruchalla, Rebecca S., Gupta, Ruchi S., Khurana Hershey, Gurjit K., Jackson, Daniel J., Kattan, Meyer, Liu, Andrew, O'Connor, George T., Rivera-Spoljaric, Katherine, Phipatanakul, Wanda, Rothenberg, Marc E., Seibold, Max A., Seroogy, Christine M., Teach, Stephen J., Zoratti, Edward M., Togias, Alkis, and Hartert, Tina V.

Published
2025
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5. Assessing the contribution of rare genetic variants to phenotypes of chronic obstructive pulmonary disease using whole-genome sequence data

Author

Kim, Wonji, Hecker, Julian, Barr, R Graham, Boerwinkle, Eric, Cade, Brian, Correa, Adolfo, Dupuis, Josée, Gharib, Sina A, Lange, Leslie, London, Stephanie J, Morrison, Alanna C, O'Connor, George T, Oelsner, Elizabeth C, Psaty, Bruce M, Vasan, Ramachandran S, Redline, Susan, Rich, Stephen S, Rotter, Jerome I, Yu, Bing, Lange, Christoph, Manichaikul, Ani, Zhou, Jin J, Sofer, Tamar, Silverman, Edwin K, Qiao, Dandi, Cho, Michael H, and Group, NHLBI Trans-Omics in Precision Medicine Consortium and TOPMed Lung Working

Subjects
Biological Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Lung, Human Genome, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Generic health relevance, Respiratory, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Genome-Wide Association Study, Phenotype, NHLBI Trans-Omics in Precision Medicine (TOPMed) Consortium and TOPMed Lung Working Group, Medical and Health Sciences, Genetics & Heredity
Abstract

RationaleGenetic variation has a substantial contribution to chronic obstructive pulmonary disease (COPD) and lung function measurements. Heritability estimates using genome-wide genotyping data can be biased if analyses do not appropriately account for the nonuniform distribution of genetic effects across the allele frequency and linkage disequilibrium (LD) spectrum. In addition, the contribution of rare variants has been unclear.ObjectivesWe sought to assess the heritability of COPD and lung function using whole-genome sequence data from the Trans-Omics for Precision Medicine program.MethodsUsing the genome-based restricted maximum likelihood method, we partitioned the genome into bins based on minor allele frequency and LD scores and estimated heritability of COPD, FEV1% predicted and FEV1/FVC ratio in 11 051 European ancestry and 5853 African-American participants.Measurements and main resultsIn European ancestry participants, the estimated heritability of COPD, FEV1% predicted and FEV1/FVC ratio were 35.5%, 55.6% and 32.5%, of which 18.8%, 19.7%, 17.8% were from common variants, and 16.6%, 35.8%, and 14.6% were from rare variants. These estimates had wide confidence intervals, with common variants and some sets of rare variants showing a statistically significant contribution (P-value

Published
2022

8. Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

Author

Hu, Xiaowei, Qiao, Dandi, Kim, Wonji, Moll, Matthew, Balte, Pallavi P, Lange, Leslie A, Bartz, Traci M, Kumar, Rajesh, Li, Xingnan, Yu, Bing, Cade, Brian E, Laurie, Cecelia A, Sofer, Tamar, Ruczinski, Ingo, Nickerson, Deborah A, Muzny, Donna M, Metcalf, Ginger A, Doddapaneni, Harshavardhan, Gabriel, Stacy, Gupta, Namrata, Dugan-Perez, Shannon, Cupples, L Adrienne, Loehr, Laura R, Jain, Deepti, Rotter, Jerome I, Wilson, James G, Psaty, Bruce M, Fornage, Myriam, Morrison, Alanna C, Vasan, Ramachandran S, Washko, George, Rich, Stephen S, O’Connor, George T, Bleecker, Eugene, Kaplan, Robert C, Kalhan, Ravi, Redline, Susan, Gharib, Sina A, Meyers, Deborah, Ortega, Victor, Dupuis, Josée, London, Stephanie J, Lappalainen, Tuuli, Oelsner, Elizabeth C, Silverman, Edwin K, Barr, R Graham, Thornton, Timothy A, Wheeler, Heather E, Group, TOPMed Lung Working, Cho, Michael H, Im, Hae Kyung, and Manichaikul, Ani

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Lung, Prevention, Tobacco, Chronic Obstructive Pulmonary Disease, Tobacco Smoke and Health, Respiratory, Good Health and Well Being, Humans, National Heart, Lung, and Blood Institute (U.S.), Pulmonary Disease, Chronic Obstructive, Risk Factors, Transcriptome, United States, TOPMed Lung Working Group, cross-ethnic portability, gene expression, integrative analysis, polygenic transcriptome risk score, pulmonary disease, risk prediction, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p

Published
2022

9. Early-life nasal microbiota dynamics relate to longitudinal respiratory phenotypes in urban children

Author

McCauley, Kathryn E., Durack, Juliana, Lynch, Kole V., Fadrosh, Douglas W., Fujimura, Kei E., Vundla, Faith, Özçam, Mustafa, LeBeau, Petra, Caltroni, Agustin, Burns, Preston, Tran, Hoang T., Bacharier, Leonard B., Kattan, Meyer, O’Connor, George T., Wood, Robert A., Togias, Alkis, Boushey, Homer A., Jackson, Daniel J., Gern, James E., and Lynch, Susan V.

Published
2024
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10. Geographic Variation in Obesity at the State Level in the All of Us Research Program

Author

Clark, Cheryl R, Chandler, Paulette D, Zhou, Guohai, Noel, Nyia, Achilike, Confidence, Mendez, Lizette, O’Connor, George T, Smoller, Jordan W, Weiss, Scott T, Murphy, Shawn N, Ommerborn, Mark J, Karnes, Jason H, Klimentidis, Yann C, Jordan, Christina D, Hiatt, Robert A, Ramirez, Andrea H, Loperena, Roxana, Mayo, Kelsey, Cohn, Elizabeth, Ohno-Machado, Lucila, Boerwinkle, Eric, Cicek, Mine, Schully, Sheri D, Mockrin, Stephen, Gebo, Kelly A, and Karlson, Elizabeth W

Subjects
Health Services and Systems, Public Health, Health Sciences, Nutrition, Obesity, Prevention, Networking and Information Technology R&D (NITRD), Stroke, Cancer, Cardiovascular, Oral and gastrointestinal, Metabolic and endocrine, Good Health and Well Being, Body Mass Index, Humans, Obesity, Morbid, Population Health, Prevalence, United States, Public Health and Health Services, Epidemiology, Health services and systems, Public health
Abstract

IntroductionNational obesity prevention strategies may benefit from precision health approaches involving diverse participants in population health studies. We used cohort data from the National Institutes of Health All of Us Research Program (All of Us) Researcher Workbench to estimate population-level obesity prevalence.MethodsTo estimate state-level obesity prevalence we used data from physical measurements made during All of Us enrollment visits and data from participant electronic health records (EHRs) where available. Prevalence estimates were calculated and mapped by state for 2 categories of body mass index (BMI) (kg/m2): obesity (BMI >30) and severe obesity (BMI >35). We calculated and mapped prevalence by state, excluding states with fewer than 100 All of Us participants.ResultsData on height and weight were available for 244,504 All of Us participants from 33 states, and corresponding EHR data were available for 88,840 of these participants. The median and IQR of BMI taken from physical measurements data was 28.4 (24.4- 33.7) and 28.5 (24.5-33.6) from EHR data, where available. Overall obesity prevalence based on physical measurements data was 41.5% (95% CI, 41.3%-41.7%); prevalence of severe obesity was 20.7% (95% CI, 20.6-20.9), with large geographic variations observed across states. Prevalence estimates from states with greater numbers of All of Us participants were more similar to national population-based estimates than states with fewer participants.ConclusionAll of Us participants had a high prevalence of obesity, with state-level geographic variation mirroring national trends. The diversity among All of Us participants may support future investigations on obesity prevention and treatment in diverse populations.

Published
2021

11. Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma

Author

Clay, Selene, Alladina, Jehan, Smith, Neal P., Visness, Cynthia M., Wood, Robert A., O’Connor, George T., Cohen, Robyn T., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Kim, Haejin, Kattan, Meyer, Bacharier, Leonard B., Rastogi, Deepa, Rivera-Spoljaric, Katherine, Robison, Rachel G., Gergen, Peter J., Busse, William W., Villani, Alexandra-Chloe, Cho, Josalyn L., Medoff, Benjamin D., Gern, James E., Jackson, Daniel J., Ober, Carole, and Dapas, Matthew

Published
2024
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15. Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.

Author

Zhao, Xutong, Qiao, Dandi, Yang, Chaojie, Kasela, Silva, Kim, Wonji, Ma, Yanlin, Shrine, Nick, Batini, Chiara, Sofer, Tamar, Taliun, Sarah A Gagliano, Sakornsakolpat, Phuwanat, Balte, Pallavi P, Prokopenko, Dmitry, Yu, Bing, Lange, Leslie A, Dupuis, Josée, Cade, Brian E, Lee, Jiwon, Gharib, Sina A, Daya, Michelle, Laurie, Cecelia A, Ruczinski, Ingo, Cupples, L Adrienne, Loehr, Laura R, Bartz, Traci M, Morrison, Alanna C, Psaty, Bruce M, Vasan, Ramachandran S, Wilson, James G, Taylor, Kent D, Durda, Peter, Johnson, W Craig, Cornell, Elaine, Guo, Xiuqing, Liu, Yongmei, Tracy, Russell P, Ardlie, Kristin G, Aguet, François, VanDenBerg, David J, Papanicolaou, George J, Rotter, Jerome I, Barnes, Kathleen C, Jain, Deepti, Nickerson, Deborah A, Muzny, Donna M, Metcalf, Ginger A, Doddapaneni, Harshavardhan, Dugan-Perez, Shannon, Gupta, Namrata, Gabriel, Stacey, Rich, Stephen S, O'Connor, George T, Redline, Susan, Reed, Robert M, Laurie, Cathy C, Daviglus, Martha L, Preudhomme, Liana K, Burkart, Kristin M, Kaplan, Robert C, Wain, Louise V, Tobin, Martin D, London, Stephanie J, Lappalainen, Tuuli, Oelsner, Elizabeth C, Abecasis, Goncalo R, Silverman, Edwin K, Barr, R Graham, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Lung Working Group, Cho, Michael H, and Manichaikul, Ani

Subjects
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Lung Working Group, Lung, Humans, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Intracellular Signaling Peptides and Proteins, Calcium-Binding Proteins, Small Ubiquitin-Related Modifier Proteins, Follow-Up Studies, Feasibility Studies, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, African Americans, Female, Male, Protein Inhibitors of Activated STAT, Respiratory Physiological Phenomena, Genome-Wide Association Study, Genetic Loci, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Whole Genome Sequencing, and over, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.

Published
2020

16. Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Author

Ober, Carole, McKennan, Chris G, Magnaye, Kevin M, Altman, Matthew C, Washington, Charles, Stanhope, Catherine, Naughton, Katherine A, Rosasco, Mario G, Bacharier, Leonard B, Billheimer, Dean, Gold, Diane R, Gress, Lisa, Hartert, Tina, Havstad, Suzanne, Hershey, Gurjit K Khurana, Hallmark, Brian, Hogarth, D Kyle, Jackson, Daniel J, Johnson, Christine C, Kattan, Meyer, Lemanske, Robert F, Lynch, Susan V, Mendonca, Eneida A, Miller, Rachel L, Naureckas, Edward T, O'Connor, George T, Seroogy, Christine M, Wegienka, Ganesa, White, Steven R, Wood, Robert A, Wright, Anne L, Zoratti, Edward M, Martinez, Fernando D, Ownby, Dennis, Nicolae, Dan L, Levin, Albert M, Gern, James E, Achten, Niek, Ainsworth, John, Akkerman, Nonna, Anderson, Elizabeth, Anderson, Larry J, Andrews, Howard, Armagost, Elizabeth, Aubuchon, Mary Ann, Bach, Julia, Bacharier, Leonard, Barnes, Kathrine L, Barone, Charles, Bauer, Irma, Beamer, Paloma, Becker, Patrice, Bednarek, Alyssa, Bellemore, Stacey, Bendixsen, Casper G, Myers, Jocelyn M Biagini, Billstrand, Christine, Birg, Geraldine, Blocki, Shirley, Bloomberg, Gordon, Bobbitt, Kevin, Bochkov, Yury, Bourgeois, Karen, Boushey, Homer, Brockman-Schneider, Rebecca, Brunwasser, Steven M, Budrevich, Richard, Burkle, Jeffrey W, Busse, William, Calatroni, Agustin, Campbell, Janice, Carlson-Dakes, Kirsten, Cassidy-Bushrow, Andrea, Chappell, James D, Chasman, Deborah, Chipps, Teresa M, Chirkova, Tatiana, Cole, Deanna, Connolly, Alexandra, Cootauco, Michelle, Costello, Kaitlin, Couch, Philip, Coull, Brent, Craven, Mark, Crisafi, Gina, Cruikshank, William, Curtsinger, Kristi, Custovic, Adnan, Das, Suman R, DaSilva, Douglas, Datta, Soma, Davidson, Brent, De La Ossa, Lydia, DeVries, Mark, Di, Qian, Dixon, Samara, Donnerbauer, Erin, and Dorst, Marian

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Lung, Clinical Research, Pediatric, Asthma, Genetics, 2.1 Biological and endogenous factors, Inflammatory and immune system, Respiratory, Black or African American, Child, Chromosomes, Human, Pair 17, Epithelial Cells, Female, Gene Expression Profiling, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Leukocytes, Mononuclear, Linkage Disequilibrium, Male, Membrane Proteins, Neoplasm Proteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, United States, White People, Environmental Influences on Child Health Outcomes-Children's Respiratory Research Workgroup, Public Health and Health Services, Other Medical and Health Sciences, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAfrican ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12-21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12-21 locus.MethodsWe first did a genetic association study and meta-analysis using 17q12-21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12-21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12-21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA).Findings17q12-21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Published
2020

17. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Published
2023
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18. Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P., Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Daniel, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J.F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A., Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Pleiness, Jacob, Pollin, Toni, Post, Wendy, Powers Becker, Julia, Preethi Boorgula, Meher, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T., Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Williams, Scott, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Baojun, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Recto, Kathryn, Kachroo, Priyadarshini, Huan, Tianxiao, Lee, Gha Young, Bui, Helena, Lee, Dong Heon, Gereige, Jessica, Yao, Chen, Hwang, Shih-Jen, Joehanes, Roby, O’Connor, George T., and DeMeo, Dawn L.

Published
2023
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20. A functional genomics pipeline to identify high-value asthma and allergy CpGs in the human methylome

Author

Morin, Andréanne, Thompson, Emma E., Helling, Britney A., Shorey-Kendrick, Lyndsey E., Faber, Pieter, Gebretsadik, Tebeb, Bacharier, Leonard B., Kattan, Meyer, O’Connor, George T., Rivera-Spoljaric, Katherine, Wood, Robert A., Barnes, Kathleen C., Mathias, Rasika A., Altman, Matthew C., Hansen, Kasper, McEvoy, Cindy T., Spindel, Eliot R., Hartert, Tina, Jackson, Daniel J., Gern, James E., McKennan, Chris G., and Ober, Carole

Published
2023
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22. Bik promotes proteasomal degradation to control low-grade inflammation

Author

Mebratu, Yohannes A., Jones, Jane T., Liu, Congjian, Negasi, Zerihun H., Rahman, Mizanur, Rojas-Quintero, Joselyn, O'Connor, George T., Gao, Wei, Dupuis, Josee, Cho, Michael H., Litonjua, Augusto A., Randell, Scott, and Tesfaigzi, Yohannes

Subjects
Physiological aspects, Development and progression, Genetic aspects, Health aspects, Emphysema -- Development and progression, Inflammation -- Development and progression, Apoptotic proteins -- Physiological aspects -- Health aspects, Proteolysis -- Health aspects -- Genetic aspects, Emphysema, Pulmonary -- Development and progression
Abstract

Introduction Inflammation is part of many important defense mechanisms that are necessary to protect the host from both infections and other environmental insults. Several highly conserved pathways orchestrate the onset [...], Although chronic low-grade inflammation does not cause immediate clinical symptoms, over the longer term, it can enhance other insults or age-dependent damage to organ systems and thereby contribute to age-related disorders, such as respiratory disorders, heart disease, metabolic disorders, autoimmunity, and cancer. However, the molecular mechanisms governing low-level inflammation are largely unknown. We discovered that Bcl-2-interacting killer (Bik) deficiency causes low- level inflammation even at baseline and the development of spontaneous emphysema in female but not male mice. Similarly, a single nucleotide polymorphism that reduced Bik levels was associated with increased inflammation and enhanced decline in lung function in humans. Transgenic expression of Bik in the airways of B/'/c- deficient mice inhibited allergen- or LPS- induced lung inflammation and reversed emphysema in female mice. Bik deficiency increased nuclear but not cytosolic p65 levels because Bik, by modifying the BH4 domain of Bcl-2, interacted with regulatory particle non-ATPase 1 (RPN1) and RPN2 and enhanced proteasomal degradation of nuclear proteins. Bik deficiency increased inflammation primarily in females because Bcl-2 and Bik levels were reduced in lung tissues and airway cells of female compared with male mice. Therefore, controlling low-grade inflammation by modifying the unappreciated role of Bik and Bcl-2 in facilitating proteasomal degradation of nuclear proteins may be crucial in treating chronic age-related diseases.

Published
2024
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24. Associations between outdoor air pollutants and non-viral asthma exacerbations and airway inflammatory responses in children and adolescents living in urban areas in the USA: a retrospective secondary analysis

Author

Altman, Matthew C, Kattan, Meyer, O'Connor, George T, Murphy, Ryan C, Whalen, Elizabeth, LeBeau, Petra, Calatroni, Agustin, Gill, Michelle A, Gruchalla, Rebecca S, Liu, Andrew H, Lovinsky-Desir, Stephanie, Pongracic, Jacqueline A, Kercsmar, Carolyn M, Khurana Hershey, Gurjit K, Zoratti, Edward M, Teach, Stephen J, Bacharier, Leonard B, Wheatley, Lisa M, Sigelman, Steve M, Gergen, Peter J, Togias, Alkis, Busse, William W, Gern, James E, and Jackson, Daniel J

Published
2023
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25. Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Published
2023
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26. Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis

Author

Hobbs, Brian D, Putman, Rachel K, Araki, Tetsuro, Nishino, Mizuki, Gudmundsson, Gunnar, Gudnason, Vilmundur, Eiriksdottir, Gudny, Nogueira, Nuno Rodrigues Zilhao, Dupuis, Josée, Xu, Hanfei, O’Connor, George T, Manichaikul, Ani, Nguyen, Jennifer, Podolanczuk, Anna J, Madahar, Purnema, Rotter, Jerome I, Lederer, David J, Barr, R Graham, Rich, Stephen S, Ampleford, Elizabeth J, Ortega, Victor E, Peters, Stephen P, O’Neal, Wanda K, Newell, John D, Bleecker, Eugene R, Meyers, Deborah A, Allen, Richard J, Oldham, Justin M, Ma, Shwu-Fan, Noth, Imre, Jenkins, R Gisli, Maher, Toby M, Hubbard, Richard B, Wain, Louise V, Fingerlin, Tasha E, Schwartz, David A, Washko, George R, Rosas, Ivan O, Silverman, Edwin K, Hatabu, Hiroto, Cho, Michael H, and Hunninghake, Gary M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Biomedical Imaging, Chronic Obstructive Pulmonary Disease, Women's Health, Prevention, Lung, Clinical Research, Rare Diseases, Genetics, Autoimmune Disease, Human Genome, 2.1 Biological and endogenous factors, Respiratory, Aged, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial, Male, Middle Aged, Mucin-5B, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, TATA Box Binding Protein-Like Proteins, beta Karyopherins, genetics, genome-wide association study, interstitial lung abnormalities, idiopathic pulmonary fibrosis, SNP, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P

Published
2019

28. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial

Author

Jackson, Daniel J, Bacharier, Leonard B, Gergen, Peter J, Gagalis, Lisa, Calatroni, Agustin, Wellford, Stephanie, Gill, Michelle A, Stokes, Jeffrey, Liu, Andrew H, Gruchalla, Rebecca S, Cohen, Robyn T, Makhija, Melanie, Khurana Hershey, Gurjit K, O'Connor, George T, Pongracic, Jacqueline A, Sherenian, Michael G, Rivera-Spoljaric, Katherine, Zoratti, Edward M, Teach, Stephen J, Kattan, Meyer, Dutmer, Cullen M, Kim, Haejin, Lamm, Carin, Sheehan, William J, Segnitz, R Max, Dill-McFarland, Kimberly A, Visness, Cynthia M, Becker, Patrice M, Gern, James E, Sorkness, Christine A, Busse, William W, and Altman, Matthew C

Published
2022
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29. The All of Us Research Program: Data quality, utility, and diversity

Author

Ahmedani, Brian, Cole Johnson, Christine D., Ahsan, Habib, Antoine-LaVigne, Donna, Singleton, Glendora, Anton-Culver, Hoda, Topol, Eric, Baca-Motes, Katie, Steinhubl, Steven, Wade, James, Begale, Mark, Jain, Praduman, Sutherland, Scott, Lewis, Beth, Korf, Bruce, Behringer, Melissa, Gharavi, Ali G., Goldstein, David B., Hripcsak, George, Bier, Louise, Boerwinkle, Eric, Brilliant, Murray H., Murali, Narayana, Hebbring, Scott Joseph, Farrar-Edwards, Dorothy, Burnside, Elizabeth, Drezner, Marc K., Taylor, Amy, Channamsetty, Veena, Montalvo, Wanda, Sharma, Yashoda, Chinea, Carmen, Jenks, Nancy, Cicek, Mine, Thibodeau, Steve, Holmes, Beverly Wilson, Schlueter, Eric, Collier, Ever, Winkler, Joyce, Corcoran, John, D’Addezio, Nick, Daviglus, Martha, Winn, Robert, Wilkins, Consuelo, Roden, Dan, Denny, Joshua, Doheny, Kim, Nickerson, Debbie, Eichler, Evan, Jarvik, Gail, Funk, Gretchen, Philippakis, Anthony, Rehm, Heidi, Lennon, Niall, Kathiresan, Sekar, Gabriel, Stacey, Gibbs, Richard, Gil Rico, Edgar M., Glazer, David, Grand, Joannie, Greenland, Philip, Harris, Paul, Shenkman, Elizabeth, Hogan, William R., Igho-Pemu, Priscilla, Pollan, Cliff, Jorge, Milena, Okun, Sally, Karlson, Elizabeth W., Smoller, Jordan, Murphy, Shawn N., Ross, Margaret Elizabeth, Kaushal, Rainu, Winford, Eboni, Wallace, Febe, Khatri, Parinda, Kheterpal, Vik, Ojo, Akinlolu, Moreno, Francisco A., Kron, Irving, Peterson, Rachele, Menon, Usha, Lattimore, Patricia Watkins, Leviner, Noga, Obedin-Maliver, Juno, Lunn, Mitchell, Malik-Gagnon, Lynda, Mangravite, Lara, Marallo, Adria, Marroquin, Oscar, Visweswaran, Shyam, Reis, Steven, Marshall, Gailen, Jr., McGovern, Patrick, Mignucci, Deb, Moore, John, Munoz, Fatima, Talavera, Gregory, O'Connor, George T., O'Donnell, Christopher, Ohno-Machado, Lucila, Orr, Greg, Randal, Fornessa, Theodorou, Andreas A., Reiman, Eric, Roxas-Murray, Mercedita, Stark, Louisa, Tepp, Ronnie, Zhou, Alicia, Topper, Scott, Trousdale, Rhonda, Tsao, Phil, Weidman, Lisa, Weiss, Scott T., Wellis, David, Whittle, Jeffrey, Wilson, Amanda, Zuchner, Stephan, Zwick, Michael E., Ramirez, Andrea H., Sulieman, Lina, Schlueter, David J., Halvorson, Alese, Qian, Jun, Ratsimbazafy, Francis, Loperena, Roxana, Mayo, Kelsey, Basford, Melissa, Deflaux, Nicole, Muthuraman, Karthik N., Natarajan, Karthik, Kho, Abel, Xu, Hua, Clark, Cheryl R., Cohn, Elizabeth, Schully, Sheri D., Ahmedani, Brian K., Argos, Maria, Cronin, Robert M., O’Donnell, Christopher, Fouad, Mona, Hebbring, Scott J., Smoller, Jordan W., Sodeke, Stephen, Wilbanks, John, Hentges, Justin, Mockrin, Stephen, Lunt, Christopher, Devaney, Stephanie A., Gebo, Kelly, Denny, Joshua C., Carroll, Robert J., Harris, Paul A., and Roden, Dan M.

Published
2022
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30. Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study

Author

Seibold, Max A., Moore, Camille M., Everman, Jamie L., Williams, Blake J.M., Nolin, James D., Fairbanks-Mahnke, Ana, Plender, Elizabeth G., Patel, Bhavika B., Arbes, Samuel J., Bacharier, Leonard B., Bendixsen, Casper G., Calatroni, Agustin, Camargo, Carlos A., Jr., Dupont, William D., Furuta, Glenn T., Gebretsadik, Tebeb, Gruchalla, Rebecca S., Gupta, Ruchi S., Khurana Hershey, Gurjit K., Murrison, Liza Bronner, Jackson, Daniel J., Johnson, Christine C., Kattan, Meyer, Liu, Andrew H., Lussier, Stephanie J., O’Connor, George T., Rivera-Spoljaric, Katherine, Phipatanakul, Wanda, Rothenberg, Marc E., Seroogy, Christine M., Teach, Stephen J., Zoratti, Edward M., Togias, Alkis, Fulkerson, Patricia C., and Hartert, Tina V.

Published
2022
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32. Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations

Author

McCauley, Kathryn E., Flynn, Kaitlin, Calatroni, Agustin, DiMassa, Vincent, LaMere, Brandon, Fadrosh, Douglas W., Lynch, Kole V., Gill, Michelle A., Pongracic, Jacqueline A., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Liu, Andrew H., Johnson, Christine C., Kim, Haejin, Kattan, Meyer, O’Connor, George T., Bacharier, Leonard B., Teach, Stephen J., Gergen, Peter J., Wheatley, Lisa M., Togias, Alkis, LeBeau, Petra, Presnell, Scott, Boushey, Homer A., Busse, William W., Gern, James E., Jackson, Daniel J., Altman, Matthew C., and Lynch, Susan V.

Published
2022
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33. Low Lung Function Is Associated with High Population Attributable Fraction for Cardiovascular Mortality.

Author

Bhatt, Surya P., Wu, Chaoqi, Sun, Yifei, Balte, Pallavi P., Schwartz, Joseph E., Divo, Miguel J., Jaeger, Byron C., Chaves, Paulo H., Couper, David, Jacobs Jr., David R., Lloyd-Jones, Donald, Kalhan, Ravi, Newman, Anne B., O'Connor, George T., Umans, Jason G., White, Wendy B., Yende, Sachin, and Oelsner, Elizabeth C.

Abstract

Rationale: Chronic lung diseases are associated with increased risk of mortality due to coronary heart disease (CHD). Nonetheless, the population attributable fraction (PAF) of lung function impairment relative to other established cardiovascular risk factors is unclear. Objectives: To evaluate the PAF of low lung function for CHD mortality Methods: We harmonized and pooled lung function and clinical data across eight U.S. general population cohorts. Impaired lung function was defined as forced expiratory volume in 1 second (FEV1) and/or forced vital capacity ≤ 95% predicted on baseline spirometry. The association between CHD mortality and risk factors was assessed using cause-specific proportional hazards and Fine-Gray proportional subdistribution hazard models, treating non-CHD mortality as a competing risk. Models were adjusted for lung function as well as age, sex, race/ethnicity, educational attainment, body mass index, smoking status, pack-years of smoking, diabetes mellitus, high-density lipoprotein, and high low-density lipoprotein (≥130 mg/dl). PAF was calculated as the relative change in the average absolute risk of 10-year CHD mortality by elimination of lung function lower than 95% predicted. Results: Among 35,143 participants, 1,844 of 13,174 (14.0%) deaths were due to CHD. Compared with percentage predicted FEV1 (FEV1pp) > 95%, the subdistribution adjusted hazard ratio for low FEV1pp was 1.30 (95% confidence interval, 1.18–1.44). The PAF for FEV1pp ≤ 95% was 12%, ranking low FEV1 third on the list of PAF for CHD mortality, after hypertension and diabetes. Low FEV1pp ranked second in the subgroup of active smokers (PAF 14%), after hypertension. Conclusions: Low lung function, even in the range considered clinically normal, ranks high on the list of attributable risk factors for CHD mortality and should be considered in cardiovascular risk stratification. [ABSTRACT FROM AUTHOR]

Published
2025
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35. Albuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study

Author

Oelsner, Elizabeth C, Balte, Pallavi P, Grams, Morgan E, Cassano, Patricia A, Jacobs, David R, Barr, R Graham, Burkart, Kristin M, Kalhan, Ravi, Kronmal, Richard, Loehr, Laura R, O'Connor, George T, Schwartz, Joseph E, Shlipak, Michael, Tracy, Russell P, Tsai, Michael Y, White, Wendy, and Yende, Sachin

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Lung, Women's Health, Health Disparities, Chronic Obstructive Pulmonary Disease, Minority Health, 4.1 Discovery and preclinical testing of markers and technologies, Cardiovascular, Respiratory, Good Health and Well Being, Aged, Albuminuria, Cohort Studies, Comorbidity, Female, Humans, Incidence, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Risk Factors, United States, epidemiology, spirometry, asthma, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

RationaleChronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.ObjectivesTo test whether albuminuria was associated with lung function decline and incident CLRDs.MethodsSix U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.Measurements and main resultsAmong 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P

Published
2019

36. Association of clonal hematopoiesis with chronic obstructive pulmonary disease

Author

Miller, Peter G., Qiao, Dandi, Rojas-Quintero, Joselyn, Honigberg, Michael C., Sperling, Adam S., Gibson, Christopher J., Bick, Alexander G., Niroula, Abhishek, McConkey, Marie E., Sandoval, Brittany, Miller, Brian C., Shi, Weiwei, Viswanathan, Kaushik, Leventhal, Matthew, Werner, Lillian, Moll, Matthew, Cade, Brian E., Barr, R. Graham, Correa, Adolfo, Cupples, L. Adrienne, Gharib, Sina A., Jain, Deepti, Gogarten, Stephanie M., Lange, Leslie A., London, Stephanie J., Manichaikul, Ani, O'Connor, George T., Oelsner, Elizabeth C., Redline, Susan, Rich, Stephen S., Rotter, Jerome I., Ramachandran, Vasan, Yu, Bing, Sholl, Lynette, Neuberg, Donna, Jaiswal, Siddhartha, Levy, Bruce D., Owen, Caroline A., Natarajan, Pradeep, Silverman, Edwin K., van Galen, Peter, Tesfaigzi, Yohannes, Cho, Michael H., and Ebert, Benjamin L.

Published
2022
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37. Inducible expression quantitative trait locus analysis of the MUC5AC gene in asthma in urban populations of children

Author

Altman, Matthew C., Flynn, Kaitlin, Rosasco, Mario G., Dapas, Matthew, Kattan, Meyer, Lovinsky-Desir, Stephanie, O’Connor, George T., Gill, Michelle A., Gruchalla, Rebecca S., Liu, Andrew H., Pongracic, Jacqueline A., Khurana Hershey, Gurjit K., Zoratti, Edward M., Teach, Stephen J., Rastrogi, Deepa, Wood, Robert A., Bacharier, Leonard B., LeBeau, Petra, Gergen, Peter J., Togias, Alkis, Busse, William W., Presnell, Scott, Gern, James E., Ober, Carole, and Jackson, Daniel J.

Published
2021
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41. African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Author

Washington, III, Charles, Dapas, Matthew, Biddanda, Arjun, Magnaye, Kevin M., Aneas, Ivy, Helling, Britney A., Szczesny, Brooke, Boorgula, Meher Preethi, Taub, Margaret A., Kenny, Eimear, Mathias, Rasika A., Barnes, Kathleen C., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gereige, Jessica D., Makhija, Melanie, Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Rastogi, Deepa, Busse, William, Gergen, Peter J., Visness, Cynthia M., Gold, Diane R., Hartert, Tina, Johnson, Christine C., Lemanske, Jr., Robert F., Martinez, Fernando D., Miller, Rachel L., Ownby, Dennis, Seroogy, Christine M., Wright, Anne L., Zoratti, Edward M., Bacharier, Leonard B., Kattan, Meyer, O’Connor, George T., Wood, Robert A., Nobrega, Marcelo A., Altman, Matthew C., Jackson, Daniel J., Gern, James E., McKennan, Christopher G., and Ober, Carole

Published
2022
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47. Genetically Predicted Body Mass Index and Mortality in Chronic Obstructive Pulmonary Disease.

Author

Zhang, Jingzhou, Moll, Matthew, Hobbs, Brian D., Bakke, Per, Regan, Elizabeth A., Xu, Hanfei, Dupuis, Josée, Chiles, Joe W., McDonald, Merry-Lynn N., Divo, Miguel J., Silverman, Edwin K., Celli, Bartolome R., O'Connor, George T., and Cho, Michael H.

Subjects
CHRONIC obstructive pulmonary disease, BODY mass index, GENETIC epidemiology, DEATH rate, MORTALITY
Abstract

Rationale: Body mass index (BMI) is associated with chronic obstructive pulmonary disease (COPD) mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate the causal mechanisms and predict risk. Objectives: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD. Methods: We developed a polygenic score (PGS) for BMI (PGSBMI) and tested for associations of the PGSBMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene (Genetic Epidemiology of COPD), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMIdiff) and categorized participants into groups of discordantly low (BMIdiff <20th percentile), concordant (BMIdiff between the 20th and 80th percentiles), and discordantly high (BMIdiff >80th percentile) BMI. We applied Cox models, examined potential nonlinear associations of the PGSBMI and BMIdiff with mortality, and summarized results with meta-analysis. Measurements and Main Results: We observed significant nonlinear associations of measured BMI and BMIdiff, but not PGSBMI, with all-cause mortality. In meta-analyses, a one–standard deviation increase in the PGSBMI was associated with an increased hazard for cardiovascular mortality (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.12–1.49), but not for respiratory or all-cause mortality. Compared with participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher risks for all-cause mortality (HR, 1.57; 95% CI, 1.41–1.74) and respiratory death (HR, 2.01; 95% CI, 1.61–2.51). Conclusions: In people with COPD, a higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with a discordantly low BMI have higher all-cause and respiratory mortality rates than those with a concordant BMI. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Author

Achten, Niek, Ainsworth, John, Akkerman, Nonna, Anderson, Elizabeth, Anderson, Larry J., Andrews, Howard, Armagost, Elizabeth, Aubuchon, Mary Ann, Bach, Julia, Bacharier, Leonard, Barnes, Kathrine L., Barone, Charles, Bauer, Irma, Beamer, Paloma, Becker, Patrice, Bednarek, Alyssa, Bellemore, Stacey, Bendixsen, Casper G., Biagini Myers, Jocelyn M., Billheimer, Dean, Billstrand, Christine, Birg, Geraldine, Blocki, Shirley, Bloomberg, Gordon, Bobbitt, Kevin, Bochkov, Yury, Bourgeois, Karen, Boushey, Homer, Brockman-Schneider, Rebecca, Brunwasser, Steven M., Budrevich, Richard, Burkle, Jeffrey W., Busse, William, Calatroni, Agustin, Campbell, Janice, Carlson-Dakes, Kirsten, Cassidy-Bushrow, Andrea, Chappell, James D., Chasman, Deborah, Chipps, Teresa M., Chirkova, Tatiana, Cole, Deanna, Connolly, Alexandra, Cootauco, Michelle, Costello, Kaitlin, Couch, Philip, Coull, Brent, Craven, Mark, Crisafi, Gina, Cruikshank, William, Curtsinger, Kristi, Custovic, Adnan, Das, Suman R., DaSilva, Douglas, Datta, Soma, Davidson, Brent, De La Ossa, Lydia, DeVries, Mark, Di, Qian, Dixon, Samara, Donnerbauer, Erin, Dorst, Marian, Doyle, Susan, Dresen, Amy, Dupont, William D., Durrange, Janet, Erickson, Heidi, Evans, Michael D., Ezell, Jerel, Farnham, Leanna, Filardo-Collins, Roxanne, Finazzo, Salvatore, Flege, Zachary, Fleurat, Conner, Floerke, Heather, Floerke, Dorothy, Foss, Terry, Freie, Angela, Frome, Wayne, Fye, Samantha, Gagalis, Lisa, Gammell, Rebecca, Gangnon, Ronald E., Ge, James E., Gebretsadik, Tebeb, Gergen, Peter, Gern, James E., Gibson, Heike, Gjerasi, Edlira, Gold, Diane R., Gonzalez, Nicole, Goodman, Kayla, Gress, Lisa, Grindle, Kristine, Groeschen, Taylor, Hallmark, Brian, Halonen, Marilyn, Hart, Jaime, Hartert, Tina V., Havstad, Suzanne, Heinritz, Patrick, Hensley Alford, Sharon, Herbstman, Julie, Hernandez, Kellie, Hoepner, Lori, Jackson, Daniel J., Jadhao, Samadhan J., Jaffee, Katy, James, Peter, Jezioro, Jacqueline, Jimenez Pescador, Marcia, Johnson, Christine C., Johnson, Tara, Johnson, Camille, Jones, Amelia, Jones, Kyra, Jones, Paul, Jordan, Carolina, Joseph, Christine LM, Kattan, Meyer, Keidel, Kristina, Keifer, Matthew C., Kelley, Rick, Khurana Hershey, Gurgit K., Kim, Haejin, Kloog, Itai, Koepel, Tammy Kronenwetter, Koerkenmeier, Clint, Ladick, Laura, Lamm, Carin, Larkin, Emma, Lederman, Howard, Lee-Parritz, Aviva, Leimenstoll, Stephanie, Lemanske, Jr., Robert F., LeMasters, Grace K., Levin, Albert M., Levine, Jessica, Liu, Xinhua, Liu, Zhouwen, Lopez, Silvia, Lothrop, Nathan, Lovinsky-Desir, Stephanie, Lukacs, Nicholas, Lynch, Susan, Lynch, Christian, Mann, Erik, Martin, Jennifer, Martin, Lisa, Martinez, Fernando D., Matsui, Elizabeth, McCauley, Katherine, Mccollum, Megan, McCullough, Judith, McKennon, Chris G., Meece, Jennifer, Mendonca, Eneida, Mikus, Lance, Miller, Rachel L., Minton, Patricia, Mitchell, Herman, Moon, Vicki, Moore, Paul E., Morgan, Wayne, Morgan, Valerie, Morgan, David, Murrison, Liza, Nicholas, Charlotte, Nicolae, Daniel, Nunez, Adam, O'Connor, George, O'Toole, Sharon, Ober, Carole, Olson, Brent F., Ong, Irene, Osmundson, Sarah, Ownby, Dennis, Pappas, Tressa, Perera, Frederica, Perzanowski, Matthew, Peterson, Edward, Pierce, Marcela, Price-Johnson, Penny, Rajamanickam, Victoria, Ramirez, Judyth, Ray, Kimberly, Renneberg, Megan, Requia, Weeberb, Riley, Kylie, Rivera, Janelle, Rivers, Neisha, Roberg, Kathy, Rogers, Theresa, Rosas-Salazar, Christian, Russell, Pat, Ryan, Patrick H., Sadovsky, Yoel, Salazar, Lisa, Sampson, Hugh, Sandel, Megan, Schoettler, Nathan, Schwartz, Joel, Scott, Dena, Seroogy, Christine M., Sharp, Renee, Shilts, Meghan H., Sigelman, Steve, Singh, Anne Marie, Sitarik, Alexandra, Smartt, Ernestine, Sorkness, Ronald, Sorkness, Christine, Spangenberg, Amber, Sperling, Rhoda, Spies, David, Stern, Debra A., Stoffel, Brandy, Peebles, R. Stokes, Stouffer, Gina, Strauchman Boyer, Cathey, Suddeuth, Caitlin, Tachinardi, Umberto, Tang, Deliang, Tang, Zhengzheng, Tate, Jena, Taylor, William, Tensing, Krista, Tesson, Elizabeth, Thompson, Kathy, Thompson, Emma, Tisler, Christopher, Togias, Alkis, Turi, Kedir, Turner, Victoria, Tuzova, Marina, VanWormer, Jeffrey J., Visness, Cynthia M., Vrtis, Rose, Wahlman, Anthony, Wang, Lena, Wegienka, Ganesa, Wells, Karen, Wentworth-Sheilds, William, Wheatley, Lisa, Whitney, Nitsa, Williams, L. Keoki, Witter, Frank, Wolfe, Christopher, Wood, Robert A., Woodcroft, Kimberley, Woodward, Kim B., Wright, Anne L., Wright, Rosalind, Wu, Pingsheng, Yaeger, Melissa, Yaniv, Perri, Zanobetti, Antonella, Zhang, Shirley, Zook, Patricia, Zoratti, Edward M., McKennan, Chris G, Magnaye, Kevin M, Altman, Matthew C, Washington, Charles, 3rd, Stanhope, Catherine, Naughton, Katherine A, Rosasco, Mario G, Bacharier, Leonard B, Gold, Diane R, Hartert, Tina, Khurana Hershey, Gurjit K, Hogarth, D Kyle, Jackson, Daniel J, Johnson, Christine C, Lemanske, Robert F, Lynch, Susan V, Mendonca, Eneida A, Miller, Rachel L, Naureckas, Edward T, O'Connor, George T, Seroogy, Christine M, White, Steven R, Wood, Robert A, Wright, Anne L, Zoratti, Edward M, Martinez, Fernando D, Nicolae, Dan L, Levin, Albert M, and Gern, James E

Published
2020
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49. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Author

Hobbs, Brian D, de Jong, Kim, Lamontagne, Maxime, Bossé, Yohan, Shrine, Nick, Artigas, María Soler, Wain, Louise V, Hall, Ian P, Jackson, Victoria E, Wyss, Annah B, London, Stephanie J, North, Kari E, Franceschini, Nora, Strachan, David P, Beaty, Terri H, Hokanson, John E, Crapo, James D, Castaldi, Peter J, Chase, Robert P, Bartz, Traci M, Heckbert, Susan R, Psaty, Bruce M, Gharib, Sina A, Zanen, Pieter, Lammers, Jan W, Oudkerk, Matthijs, Groen, HJ, Locantore, Nicholas, Tal-Singer, Ruth, Rennard, Stephen I, Vestbo, Jørgen, Timens, Wim, Paré, Peter D, Latourelle, Jeanne C, Dupuis, Josée, O'Connor, George T, Wilk, Jemma B, Kim, Woo Jin, Lee, Mi Kyeong, Oh, Yeon-Mok, Vonk, Judith M, de Koning, Harry J, Leng, Shuguang, Belinsky, Steven A, Tesfaigzi, Yohannes, Manichaikul, Ani, Wang, Xin-Qun, Rich, Stephen S, Barr, R Graham, Sparrow, David, Litonjua, Augusto A, Bakke, Per, Gulsvik, Amund, Lahousse, Lies, Brusselle, Guy G, Stricker, Bruno H, Uitterlinden, André G, Ampleford, Elizabeth J, Bleecker, Eugene R, Woodruff, Prescott G, Meyers, Deborah A, Qiao, Dandi, Lomas, David A, Yim, Jae-Joon, Kim, Deog Kyeom, Hawrylkiewicz, Iwona, Sliwinski, Pawel, Hardin, Megan, Fingerlin, Tasha E, Schwartz, David A, Postma, Dirkje S, MacNee, William, Tobin, Martin D, Silverman, Edwin K, Boezen, H Marike, and Cho, Michael H

Subjects
Biological Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Prevention, Human Genome, Lung, 2.1 Biological and endogenous factors, Respiratory, Adult, Aged, Aged, 80 and over, Alleles, Asthma, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Pulmonary Fibrosis, Risk Factors, Smoking, COPDGene Investigators, ECLIPSE Investigators, LifeLines Investigators, SPIROMICS Research Group, International COPD Genetics Network Investigators, UK BiLEVE Investigators, International COPD Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Published
2017

50. Sex-Based Genetic Association Study Identifies CELSR1 as a Possible Chronic Obstructive Pulmonary Disease Risk Locus among Women

Author

Hardin, Megan, Cho, Michael H, Sharma, Sunita, Glass, Kimberly, Castaldi, Peter J, McDonald, Merry-Lynn, Aschard, Hugues, Senter-Sylvia, Jody, Tantisira, Kelan, Weiss, Scott T, Hersh, Craig P, Morrow, Jarrett D, Lomas, David, Agusti, Alvar, Bakke, Per, Gulsvik, Amund, O'Connor, George T, Dupuis, Josée, Hokanson, John, Crapo, James D, Beaty, Terri H, Laird, Nan, Silverman, Edwin K, and DeMeo, Dawn L

Subjects
Biological Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Tobacco Smoke and Health, Prevention, Clinical Research, Lung, Tobacco, Human Genome, Respiratory, Aged, Alleles, Cadherins, Demography, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Risk Factors, chronic obstructive pulmonary disease, genetics, growth and development, sex, genome-wide association study, COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points Investigators, Cardiorespiratory Medicine and Haematology, Respiratory System, Biochemistry and cell biology, Cardiovascular medicine and haematology
Abstract

Chronic obstructive pulmonary disease (COPD) is a complex disease with strong environmental and genetic influences and sexually dimorphic features. Although genetic risk factors for COPD have been identified, much of the heritability remains unexplained. Sex-based genetic association studies may uncover additional COPD genetic risk factors. We studied current and former smokers from COPD case-control cohorts (COPDGene non-Hispanic whites and African Americans, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points, and Genetics of Chronic Obstructive Lung Disease). COPD was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity less than 0.70 and forced expiratory volume in 1 second percent predicted less than 80. Testing was performed across all cohorts and combined in a meta-analysis adjusted for age, pack-years, and genetic ancestry. We first performed genome-wide single-nucleotide polymorphism (SNP)-by-sex interaction testing on the outcome of COPD affection status. We performed sex-stratified association testing for SNPs with interaction P less than 10-6. We examined over 8 million SNPs in four populations, including 6,260 subjects with COPD (40.6% female) and 5,269 smoking control subjects (47.3% female). The SNP rs9615358 in the cadherin gene CELSR1 approached genome-wide significance for an interaction with sex (P = 1.24 × 10-7). In the sex-stratified meta-analysis, this SNP was associated with COPD among females (odds ratio, 1.37 [95% confidence interval, 1.25-1.49]; P = 3.32 × 10-7) but not males (odds ratio, 0.90 [95% confidence interval, 0.79-1.01]; P = 0.06). CELSR1 is involved in fetal lung development. In a human fetal lung tissue dataset, we observed greater CELSR1 expression in female compared with male samples. This SNP-by-sex genome-wide association analysis identified the fetal lung development gene, CELSR1, as a potential sex-specific risk factor for COPD. Identifying sex-specific genetic risk factors may reveal new insights into sexually dimorphic features of COPD.

Published
2017

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