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188 results on '"Loth, Daan W."'

1. Association of Forced Vital Capacity with the Developmental Gene NCOR2

Author

Minelli, Cosetta, Dean, Charlotte H, Hind, Matthew, Alves, Alexessander Couto, Amaral, André FS, Siroux, Valerie, Huikari, Ville, Soler Artigas, María, Evans, David M, Loth, Daan W, Bossé, Yohan, Postma, Dirkje S, Sin, Don, Thompson, John, Demenais, Florence, Henderson, John, Bouzigon, Emmanuelle, Jarvis, Deborah, Järvelin, Marjo-Riitta, and Burney, Peter

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Lung, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Adult, Aged, Female, Forced Expiratory Volume, Gene Expression Profiling, Genes, Developmental, Genetic Association Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Nuclear Receptor Co-Repressor 2, Organogenesis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Young Adult, SpiroMeta consortium, CHARGE consortium, General Science & Technology
Abstract

BackgroundForced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes.MethodsPer-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p

Published
2016

2. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce BJ, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, and Ripatti, Samuli

Subjects
Biological Sciences, Genetics, Human Genome, Rare Diseases, Lung, Cancer, Lung Cancer, Respiratory, Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Published
2014

3. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Author

Tang, Wenbo, Kowgier, Matthew, Loth, Daan W, Soler Artigas, María, Joubert, Bonnie R, Hodge, Emily, Gharib, Sina A, Smith, Albert V, Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A, Harris, Tamara B, Hansel, Nadia N, Launer, Lenore J, Barnes, Kathleen C, Hansen, Joyanna G, Albrecht, Eva, Aldrich, Melinda C, Allerhand, Michael, Barr, R Graham, Brusselle, Guy G, Couper, David J, Curjuric, Ivan, Davies, Gail, Deary, Ian J, Dupuis, Josée, Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Gläser, Sven, Gu, Xiangjun, Hancock, Dana B, Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B, Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L, Meibohm, Bernd, Morris, Andrew P, Morrison, Alanna C, Musk, Bill, North, Kari E, Palmer, Lyle J, Probst-Hensch, Nicole M, Psaty, Bruce M, Rivadeneira, Fernando, Rotter, Jerome I, Schulz, Holger, Smith, Lewis J, Sood, Akshay, Starr, John M, Strachan, David P, Teumer, Alexander, Uitterlinden, André G, Völzke, Henry, Voorman, Arend, Wain, Louise V, Wells, Martin T, Wilk, Jemma B, Williams, O Dale, Heckbert, Susan R, Stricker, Bruno H, London, Stephanie J, Fornage, Myriam, Tobin, Martin D, O'Connor, George T, Hall, Ian P, and Cassano, Patricia A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Human Genome, Lung, Clinical Research, Prevention, Respiratory, Adult, Chromosomes, Human, Pair 11, Female, Gene Expression Regulation, Genetic Loci, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Respiration, General Science & Technology
Abstract

BackgroundGenome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.MethodsWe performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.ResultsThe overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.ConclusionsIn this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Published
2014

5. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

Author

Demenais, Florence, Margaritte-Jeannin, Patricia, Barnes, Kathleen C., Cookson, William O. C., Altmüller, Janine, Ang, Wei, Barr, R. Graham, Beaty, Terri H., Becker, Allan B., Beilby, John, Bisgaard, Hans, Bjornsdottir, Unnur Steina, Bleecker, Eugene, Bønnelykke, Klaus, Boomsma, Dorret I., Bouzigon, Emmanuelle, Brightling, Christopher E., Brossard, Myriam, Brusselle, Guy G., Burchard, Esteban, Burkart, Kristin M., Bush, Andrew, Chan-Yeung, Moira, Chung, Kian Fan, Couto Alves, Alexessander, Curtin, John A., Custovic, Adnan, Daley, Denise, de Jongste, Johan C., Del-Rio-Navarro, Blanca E., Donohue, Kathleen M., Duijts, Liesbeth, Eng, Celeste, Eriksson, Johan G., Farrall, Martin, Fedorova, Yuliya, Feenstra, Bjarke, Ferreira, Manuel A., Freidin, Maxim B., Gajdos, Zofia, Gauderman, Jim, Gehring, Ulrike, Geller, Frank, Genuneit, Jon, Gharib, Sina A., Gilliland, Frank, Granell, Raquel, Graves, Penelope E., Gudbjartsson, Daniel F., Haahtela, Tari, Heckbert, Susan R., Heederik, Dick, Heinrich, Joachim, Heliövaara, Markku, Henderson, John, Himes, Blanca E., Hirose, Hiroshi, Hirschhorn, Joel N., Hofman, Albert, Holt, Patrick, Hottenga, Jouke, Hudson, Thomas J., Hui, Jennie, Imboden, Medea, Ivanov, Vladimir, Jaddoe, Vincent W. V., James, Alan, Janson, Christer, Jarvelin, Marjo-Riitta, Jarvis, Deborah, Jones, Graham, Jonsdottir, Ingileif, Jousilahti, Pekka, Kabesch, Michael, Kähönen, Mika, Kantor, David B., Karunas, Alexandra S., Khusnutdinova, Elza, Koppelman, Gerard H., Kozyrskyj, Anita L., Kreiner, Eskil, Kubo, Michiaki, Kumar, Rajesh, Kumar, Ashish, Kuokkanen, Mikko, Lahousse, Lies, Laitinen, Tarja, Laprise, Catherine, Lathrop, Mark, Lau, Susanne, Lee, Young-Ae, Lehtimäki, Terho, Letort, Sébastien, Levin, Albert M., Li, Guo, Liang, Liming, Loehr, Laura R., London, Stephanie J., Loth, Daan W., Manichaikul, Ani, Marenholz, Ingo, Martinez, Fernando J., Matheson, Melanie C., Mathias, Rasika A., Matsumoto, Kenji, Mbarek, Hamdi, McArdle, Wendy L., Melbye, Mads, Melén, Erik, Meyers, Deborah, Michel, Sven, Mohamdi, Hamida, Musk, Arthur W., Myers, Rachel A., Nieuwenhuis, Maartje A. E., Noguchi, Emiko, O’Connor, George T., Ogorodova, Ludmila M., Palmer, Cameron D., Palotie, Aarno, Park, Julie E., Pennell, Craig E., Pershagen, Göran, Polonikov, Alexey, Postma, Dirkje S., Probst-Hensch, Nicole, Puzyrev, Valery P., Raby, Benjamin A., Raitakari, Olli T., Ramasamy, Adaikalavan, Rich, Stephen S., Robertson, Colin F., Romieu, Isabelle, Salam, Muhammad T., Salomaa, Veikko, Schlünssen, Vivi, Scott, Robert, Selivanova, Polina A., Sigsgaard, Torben, Simpson, Angela, Siroux, Valérie, Smith, Lewis J., Solodilova, Maria, Standl, Marie, Stefansson, Kari, Strachan, David P., Stricker, Bruno H., Takahashi, Atsushi, Thompson, Philip J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiesler, Carla M. T., Torgerson, Dara G., Tsunoda, Tatsuhiko, Uitterlinden, André G., van der Valk, Ralf J. P., Vaysse, Amaury, Vedantam, Sailaja, von Berg, Andrea, von Mutius, Erika, Vonk, Judith M., Waage, Johannes, Wareham, Nick J., Weiss, Scott T., White, Wendy B., Wickman, Magnus, Widén, Elisabeth, Willemsen, Gonneke, Williams, L. Keoki, Wouters, Inge M., Yang, James J., Zhao, Jing Hua, Moffatt, Miriam F., Ober, Carole, and Nicolae, Dan L.

Published
2018
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6. ERS International Congress 2022:highlights from the Interstitial Lung Diseases Assembly

Author

Karampitsakos, Theodoros, Diep, Phuong Phuong, Loth, Daan W., Nadeem, Iftikhar, Khurtsidze, Elene, Wijsenbeek, Marlies S., Wuyts, Wim A., Bargagli, Elena, Froidure, Antoine, Spagnolo, Paolo, Veltkamp, Marcel, Molina-Molina, Maria, McCarthy, Cormac, Antoniou, Katerina M., Kreuter, Michael, Moor, Catharina C., Karampitsakos, Theodoros, Diep, Phuong Phuong, Loth, Daan W., Nadeem, Iftikhar, Khurtsidze, Elene, Wijsenbeek, Marlies S., Wuyts, Wim A., Bargagli, Elena, Froidure, Antoine, Spagnolo, Paolo, Veltkamp, Marcel, Molina-Molina, Maria, McCarthy, Cormac, Antoniou, Katerina M., Kreuter, Michael, and Moor, Catharina C.

Abstract

This article contains a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the hybrid European Respiratory Society International Congress 2022. Early Career Members of Assembly 12 summarise recent advances in translational and clinical research in idiopathic interstitial pneumonias, ILDs of known origin, sarcoidosis and other granulomatous diseases, and rare ILDs. Many studies focused on evaluation of diagnostic and prognostic (bio)markers, and novel pharmacological and nonpharmacological treatment options for different ILDs. In addition, new insights in clinical, physiological and radiological features of various rare ILDs were presented.

Published
2023

8. ERS International Congress 2022: highlights from the Interstitial Lung Diseases Assembly

Author

Karampitsakos, Theodoros, primary, Diep, Phuong Phuong, additional, Loth, Daan W., additional, Nadeem, Iftikhar, additional, Khurtsidze, Elene, additional, Wijsenbeek, Marlies S., additional, Wuyts, Wim A., additional, Bargagli, Elena, additional, Froidure, Antoine, additional, Spagnolo, Paolo, additional, Veltkamp, Marcel, additional, Molina-Molina, Maria, additional, McCarthy, Cormac, additional, Antoniou, Katerina M., additional, Kreuter, Michael, additional, and Moor, Catharina C., additional

Published
2023
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9. Molecular mechanisms underlying variations in lung function: a systems genetics analysis

Author

Obeidat, Ma'en, Hao, Ke, Bossé, Yohan, Nickle, David C, Nie, Yunlong, Postma, Dirkje S, Laviolette, Michel, Sandford, Andrew J, Daley, Denise D, Hogg, James C, Elliott, W Mark, Fishbane, Nick, Timens, Wim, Hysi, Pirro G, Kaprio, Jaakko, Wilson, James F, Hui, Jennie, Rawal, Rajesh, Schulz, Holger, Stubbe, Beate, Hayward, Caroline, Polasek, Ozren, Järvelin, Marjo-Riitta, Zhao, Jing Hua, Jarvis, Deborah, Kähönen, Mika, Franceschini, Nora, North, Kari E, Loth, Daan W, Brusselle, Guy G, Smith, Albert Vernon, Gudnason, Vilmundur, Bartz, Traci M, Wilk, Jemma B, O'Connor, George T, Cassano, Patricia A, Tang, Wenbo, Wain, Louise V, Artigas, María Soler, Gharib, Sina A, Strachan, David P, Sin, Don D, Tobin, Martin D, London, Stephanie J, Hall, Ian P, and Paré, Peter D

Published
2015
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10. Adverse outcomes of frailty in the elderly: the Rotterdam Study

Author

Lahousse, Lies, Maes, Bastiaan, Ziere, Gijsbertus, Loth, Daan W., Verlinden, Vincentius J. A., Zillikens, M. Carola, Uitterlinden, André G., Rivadeneira, Fernando, Tiemeier, Henning, Franco, Oscar H., Ikram, M. Arfan, Hofman, Albert, Brusselle, Guy G., and Stricker, Bruno H.

Published
2014

12. Regional Impact of COVID-19-Associated Pulmonary Aspergillosis (CAPA) during the First Wave

Author

Bentvelsen, R.G., Arkel, A.L.E. van, Rijpstra, Tom A., Kant, Merijn K.M., Brugge, Simone Van Der Sar-Van Der, Loth, Daan W., Bijllaardt, Wouter van den, Verweij, P.E., Bentvelsen, R.G., Arkel, A.L.E. van, Rijpstra, Tom A., Kant, Merijn K.M., Brugge, Simone Van Der Sar-Van Der, Loth, Daan W., Bijllaardt, Wouter van den, and Verweij, P.E.

Abstract

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Published
2022

13. TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients

Author

Assmann, Jorn L.J.C., Kolijn, P. Martijn, Schrijver, Benjamin, van Gammeren, Adriaan J., Loth, Daan W., Ermens, Ton A.A.M., Dik, Willem A., van der Velden, Vincent H.J., Langerak, Anton W., Assmann, Jorn L.J.C., Kolijn, P. Martijn, Schrijver, Benjamin, van Gammeren, Adriaan J., Loth, Daan W., Ermens, Ton A.A.M., Dik, Willem A., van der Velden, Vincent H.J., and Langerak, Anton W.

Abstract

The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 158 SARS-CoV-2 specific TRB sequences belonging to 134 clusters in our COVID-19 patients. Next, we investigated 113 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS-CoV-2 genome was observed in clusters associated with critical disease course when compared to COVID-19 clusters associated with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from NSPs of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.

Published
2022

14. Regional Impact of COVID-19-Associated Pulmonary Aspergillosis (CAPA) during the First Wave

Author

Bentvelsen, Robbert G., primary, Arkel, Andreas L. E. Van, additional, Rijpstra, Tom A., additional, Kant, Merijn K. M., additional, Brugge, Simone Van Der Sar-Van Der, additional, Loth, Daan W., additional, Van Wijngaarden, Peter, additional, Mée, Arthur W. F. Du, additional, Yick, David C. Y., additional, Diederen, Bram M. W., additional, Wever, Peter C., additional, Leenders, Alexander C. A. P., additional, Van Dommelen, Laura, additional, Groot, Klaas H. De, additional, Van den Bijllaardt, Wouter, additional, and Verweij, Paul E., additional

Published
2022
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15. Integrative pathway genomics of lung function and airflow obstruction

Author

Gharib, Sina A., Loth, Daan W., Soler Artigas, María, Birkland, Timothy P., Wilk, Jemma B., Wain, Louise V., Brody, Jennifer A., Obeidat, Maʼen, Hancock, Dana B., Tang, Wenbo, Rawal, Rajesh, Boezen, H. Marike, Imboden, Medea, Huffman, Jennifer E., Lahousse, Lies, Alves, Alexessander C., Manichaikul, Ani, Hui, Jennie, Morrison, Alanna C., Ramasamy, Adaikalavan, Smith, Albert Vernon, Gudnason, Vilmundur, Surakka, Ida, Vitart, Veronique, Evans, David M., Strachan, David P., Deary, Ian J., Hofman, Albert, Gläser, Sven, Wilson, James F., North, Kari E., Zhao, Jing Hua, Heckbert, Susan R., Jarvis, Deborah L., Probst-Hensch, Nicole, Schulz, Holger, Barr, R. Graham, Jarvelin, Marjo-Riitta, OʼConnor, George T., Kähönen, Mika, Cassano, Patricia A., Hysi, Pirro G., Dupuis, Josée, Hayward, Caroline, Psaty, Bruce M., Hall, Ian P., Parks, William C., Tobin, Martin D., and London, Stephanie J.

Published
2015
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21. Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

Author

Wilk, Jemma B., Shrine, Nick R. G., Loehr, Laura R., Zhao, Jing Hua, Manichaikul, Ani, Lopez, Lorna M., Smith, Albert Vernon, Heckbert, Susan R., Smolonska, Joanna, Tang, Wenbo, Loth, Daan W., Curjuric, Ivan, Hui, Jennie, Cho, Michael H., Latourelle, Jeanne C., Henry, Amanda P., Aldrich, Melinda, Bakke, Per, Beaty, Terri H., Bentley, Amy R., Borecki, Ingrid B., Brusselle, Guy G., Burkart, Kristin M., Chen, Ting-hsu, Couper, David, Crapo, James D., Davies, Gail, Dupuis, Josée, Franceschini, Nora, Gulsvik, Amund, Hancock, Dana B., Harris, Tamara B., Hofman, Albert, Imboden, Medea, James, Alan L., Khaw, Kay-Tee, Lahousse, Lies, Launer, Lenore J., Litonjua, Augusto, Liu, Yongmei, Lohman, Kurt K., Lomas, David A., Lumley, Thomas, Marciante, Kristin D., McArdle, Wendy L., Meibohm, Bernd, Morrison, Alanna C., Musk, Arthur W., Myers, Richard H., North, Kari E., Postma, Dirkje S., Psaty, Bruce M., Rich, Stephen S., Rivadeneira, Fernando, Rochat, Thierry, Rotter, Jerome I., Artigas, María Soler, Starr, John M., Uitterlinden, André G., Wareham, Nicholas J., Wijmenga, Cisca, Zanen, Pieter, Province, Michael A., Silverman, Edwin K., Deary, Ian J., Palmer, Lyle J., Cassano, Patricia A., Gudnason, Vilmundur, Barr, Graham R., Loos, Ruth J. F., Strachan, David P., London, Stephanie J., Boezen, Marike H., Probst-Hensch, Nicole, Gharib, Sina A., Hall, Ian P., O’Connor, George T., Tobin, Martin D., and Stricker, Bruno H.

Published
2012
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23. Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Author

Sakornsakolpat, Phuwanat, Prokopenko, Dmitry, Lamontagne, Maxime, Reeve, Nicola F., Guyatt, Anna L., Jackson, Victoria E., Shrine, Nick, Qiao, Dandi, Bartz, Traci M., Kim, Deog Kyeom, Lee, Mi Kyeong, Latourelle, Jeanne C., Li, Xingnan, Morrow, Jarrett D., Obeidat, Ma’en, Wyss, Annah B., Bakke, Per, Barr, R. Graham, Beaty, Terri H., Belinsky, Steven A., Brusselle, Guy G., Crapo, James D., de Jong, Kim, DeMeo, Dawn L., Fingerlin, Tasha E., Gharib, Sina A., Gulsvik, Amund, Hall, Ian P., Hokanson, John E., Kim, Woo Jin, Lomas, David A., London, Stephanie J., Meyers, Deborah A., O’Connor, George T., Rennard, Stephen I., Schwartz, David A., Sliwinski, Pawel, Sparrow, David, Strachan, David P., Tal-Singer, Ruth, Tesfaigzi, Yohannes, Vestbo, Jørgen, Vonk, Judith M., Yim, Jae-Joon, Zhou, Xiaobo, Bossé, Yohan, Manichaikul, Ani, Lahousse, Lies, Silverman, Edwin K., Boezen, H. Marike, Wain, Louise V., Tobin, Martin D., Hobbs, Brian D., Cho, Michael H., Batini, Chiara, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E., Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Ewert, Ralf, Gieger, Christian, Homuth, Georg, Joshi, Peter K., Langenberg, Claudia, Lind, Lars, Luan, Jian’an, Mahajan, Anubha, Murray, Alison, Porteous, David J., Rawal, Rajesh, Smith, Blair H., Timmers, Paul R. H. J., Raitakari, Olli T., Kähönen, Mika, Polasek, Ozren, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Probst-Hensch, Nicole M., Schulz, Holger, James, Alan L., Wilson, James F., Stubbe, Beate, Zeggini, Eleftheria, Jarvelin, Marjo-Riitta, Wareham, Nick, Hayward, Caroline, Morris, Andrew P., Agusti, Alvar, Anderson, Wayne, Bakerly, Nawar, Bals, Robert, Barnes, Kathleen C., Bleecker, Eugene R., Bowler, Russell, Brightling, Christopher, de Bruijne, Marleen, Castaldi, Peter J., Celli, Bartolome, Coxson, Harvey O., Crystal, Ron, de Jong, Pim, Dirksen, Asger, Dy, Jennifer, Foreman, Marilyn, Garcia-Aymerich, Judith, Gevenois, Pierre, Ghosh, Soumitra, Gietema, Hester, Hansel, Nadia, Hersh, Craig P., Hoffman, Eric, Kalsheker, Noor, Kauczor, Hans-Ulrich, Laitinen, Tarja, Lambrechts, Diether, Lee, Sang-Do, Litonjua, Augusto A., Loth, Daan W., Lutz, Sharon M., Lynch, David, MacNee, William, McDonald, Merry-Lynn, Newell, John D., Nordestgaard, Borge G., Oh, Yeon-Mok, Paré, Peter D., Pistolesi, Massimo, Postma, Dirkje S., Puhan, Milo, Regan, Elizabeth, Rich, Stephen S., Seo, Joon Beom, Short, Andrea, Stoel, Berend, Sverzellati, Nicola, ter Riet, Gerben, Van Beek, Edwin J. R., van Ginneken, Bram, Vogelmeier, Claus F., Wanner, Adam, Washko, George, Wauters, Els, Wouters, Emiel F. M., Young, Robert P., Zeigler-Heitbrock, Loems, SpiroMeta Consortium, Understanding Society Scientific Group, International COPD Genetics Consortium, Institute for Molecular Medicine Finland, Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), MUMC+: MA Longziekten (3), RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, General practice, APH - Aging & Later Life, APH - Personalized Medicine, ACS - Diabetes & metabolism, Epidemiology, Pulmonary Medicine, Medical Informatics, and Radiology & Nuclear Medicine

Subjects
Male, Lydia Becker Institute, Pulmonary Fibrosis, LD SCORE REGRESSION, Gene Expression, Genome-wide association study, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Pulmonary fibrosis, GWAS, Lung, GENOME-WIDE ASSOCIATION, ACIDIC-MAMMALIAN-CHITINASE, LUNG-FUNCTION, EXTRACELLULAR-MATRIX, PREDOMINANT EMPHYSEMA, CONNECTIVITY MAP, ATOPIC ASTHMA, RISK LOCI, 0303 health sciences, COPD, education.field_of_study, Smoking, 1184 Genetics, developmental biology, physiology, Middle Aged, 3. Good health, Phenotype, medicine.anatomical_structure, Medical genetics, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Population, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Aged, 030304 developmental biology, Asthma, medicine.disease, respiratory tract diseases, Genetic Loci, Case-Control Studies, Immunology, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD., Editorial summary Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

Published
2019

24. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Author

Aschard, Hugues, Tobin, Martin D, Hancock, Dana B., Skurnik, David, Sood, Akshay, James, Alan, Smith, Albert Vernon, Manichaikul, Ani, Campbell, Archie, Prins, Bram P, Hayward, Caroline, Loth, Daan W., Porteous, David, Strachan, David P, Zeggini, Eleftheria, O'Connor, George T., Brusselle, Guy G., Boezen, H. Marike, Schulz, Holger, Deary, Ian J, Hall, Ian P, Rudan, Igor, Kaprio, Jaakko, Wilson, James, Wilk, Jemma B., Huffman, Jennifer, Zhao, Jing Hua, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V, Jarvelin, Marjo-Riitta, Kahonen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A., Barr, R. Graham, Rawal, Rajesh, Harris, Sarah, Gharib, Sina A., Enroth, Stefan, Heckbert, Susan R., Lehtimaki, Terho, Gyllensten, Ulf, Jackson, Victoria E, Gudnason, Vilmundur, Tang, Wenbo, Dupuis, Josee, Artigas, María Soler, Joshi, Amit D, and Kraft, Peter

Subjects
respiratory system, respiratory tract diseases
Abstract

Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking.Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia.Results: We identified an interaction (βint = –0.036, 95% confidence interval, –0.040 to –0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect.Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.

Published
2017

25. Integrative pathway genomics of lung function and airflow obstruction

Author

Gharib, Sina A., Loth, Daan W., Soler Artigas, María, Birkland, Timothy P., Wilk, Jemma B., Wain, Louise V., Brody, Jennifer A., Obeidat, Ma'en, Hancock, Dana B., Tang, Wenbo, Rawal, Rajesh, Boezen, H. Marike, Imboden, Medea, Huffman, Jennifer E., Lahousse, Lies, Alves, Alexessander C., Manichaikul, Ani, Hui, Jennie, Morrison, Alanna C., Ramasamy, Adaikalavan, Smith, Albert Vernon, Gudnason, Vilmundur, Surakka, Ida, Vitart, Veronique, Evans, David M., Strachan, David P., Deary, Ian J., Hofman, Albert, Gläser, Sven, Wilson, James F., North, Kari E., Zhao, Jing Hua, Heckbert, Susan R., Jarvis, Deborah L., Probst-Hensch, Nicole, Schulz, Holger, Barr, R. Graham, Jarvelin, Marjo-Riitta, O'Connor, George T., Kähönen, Mika, Cassano, Patricia A., Hysi, Pirro G., Dupuis, Josée, Hayward, Caroline, Psaty, Bruce M., Hall, Ian P., Parks, William C., Tobin, Martin D., London, Stephanie J., Gharib, Sina A., Loth, Daan W., Soler Artigas, María, Birkland, Timothy P., Wilk, Jemma B., Wain, Louise V., Brody, Jennifer A., Obeidat, Ma'en, Hancock, Dana B., Tang, Wenbo, Rawal, Rajesh, Boezen, H. Marike, Imboden, Medea, Huffman, Jennifer E., Lahousse, Lies, Alves, Alexessander C., Manichaikul, Ani, Hui, Jennie, Morrison, Alanna C., Ramasamy, Adaikalavan, Smith, Albert Vernon, Gudnason, Vilmundur, Surakka, Ida, Vitart, Veronique, Evans, David M., Strachan, David P., Deary, Ian J., Hofman, Albert, Gläser, Sven, Wilson, James F., North, Kari E., Zhao, Jing Hua, Heckbert, Susan R., Jarvis, Deborah L., Probst-Hensch, Nicole, Schulz, Holger, Barr, R. Graham, Jarvelin, Marjo-Riitta, O'Connor, George T., Kähönen, Mika, Cassano, Patricia A., Hysi, Pirro G., Dupuis, Josée, Hayward, Caroline, Psaty, Bruce M., Hall, Ian P., Parks, William C., Tobin, Martin D., and London, Stephanie J.

Abstract

Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease

Published
2017

26. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Author

Aschard, Hugues, primary, Tobin, Martin D, additional, Hancock, Dana B, additional, Skurnik, David, additional, Sood, Akshay, additional, James, Alan, additional, Vernon Smith, Albert, additional, Manichaikul, Ani W, additional, Campbell, Archie, additional, Prins, Bram P, additional, Hayward, Caroline, additional, Loth, Daan W, additional, Porteous, David J, additional, Strachan, David P, additional, Zeggini, Eleftheria, additional, O’Connor, George T, additional, Brusselle, Guy G, additional, Boezen, H Marike, additional, Schulz, Holger, additional, Deary, Ian J, additional, Hall, Ian P, additional, Rudan, Igor, additional, Kaprio, Jaakko, additional, Wilson, James F, additional, Wilk, Jemma B, additional, Huffman, Jennifer E, additional, Hua Zhao, Jing, additional, de Jong, Kim, additional, Lyytikäinen, Leo-Pekka, additional, Wain, Louise V, additional, Jarvelin, Marjo-Riitta, additional, Kähönen, Mika, additional, Fornage, Myriam, additional, Polasek, Ozren, additional, Cassano, Patricia A, additional, Barr, R Graham, additional, Rawal, Rajesh, additional, Harris, Sarah E, additional, Gharib, Sina A, additional, Enroth, Stefan, additional, Heckbert, Susan R, additional, Lehtimäki, Terho, additional, Gyllensten, Ulf, additional, Society Scientific Group, Understanding, additional, Jackson, Victoria E, additional, Gudnason, Vilmundur, additional, Tang, Wenbo, additional, Dupuis, Josée, additional, Soler Artigas, María, additional, Joshi, Amit D, additional, London, Stephanie J, additional, and Kraft, Peter, additional

Published
2017
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27. Correction : Susceptibility to chronic mucus hypersecretion, a genome wide association study

Author

Dijkstra, Akkelies E., Smolonska, Joanna, Van Den Berge, Maarten, Wijmenga, Ciska, Zanen, Pieter, Luinge, Marjan A., Platteel, Mathieu, Lammers, Jan Willem, Dahlback, Magnus, Tosh, Kerrie, Hiemstra, Pieter S., Sterk, Peter J., Spira, Avi, Vestbo, Jorgen, Nordestgaard, Borge G., Benn, Marianne, Nielsen, Sune F., Dahl, Morten, Verschuren, W. Monique, Picavet, H. Susan J, Smit, Henriette A., Owsijewitsch, Michael, Kauczor, Hans U., De Koning, Harry J., Nizankowska-Mogilnicka, Eva, Mejza, Filip, Nastalek, Pawel, Van Diemen, Cleo C., Cho, Michael H., Silverman, Edwin K., Crapo, James D., Beaty, Terri H., Lomas, David A., Bakke, Per, Gulsvik, Amund, Bossé, Yohan, Obeidat, Ma'en, Loth, Daan W., Lahousse, Lies, Rivadeneira, Fernando, Uitterlinden, Andre G., Hofman, Andre, Stricker, Bruno H., Brusselle, Guy G., Van Duijn, Cornelia M., Brouwer, Uilke, Koppelman, Gerard H., Vonk, Judith M., Nawijn, Martijn C., Groen, Harry J M, Timens, Wim, Boezen, H. Marike, and Postma, Dirkje S.

Subjects
Medicine(all), Published Erratum, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all)
Published
2015

28. Molecular mechanisms underlying variations in lung function: a systems genetics analysis

Author

Bossé, Yohan, Nie, Yunlong, Obeidat, Ma'en, Schulz, Holger, Sandford, Andrew J, Smith, Albert Vernon, Laviolette, Michel, Daley, Denise D, Rawal, Rajesh, Hogg, James C, Hysi, Pirro G, Kähönen, Mika, Jarvis, Deborah, Hao, Ke, Gudnason, Vilmundur, Loth, Daan W, Wilson, James F, Brusselle, Guy G, Stubbe, Beate, Järvelin, Marjo-Riitta, Kaprio, Jaakko, Polasek, Ozren, Zhao, Jing Hua, North, Kari E, Fishbane, Nick, Hayward, Caroline, Elliott, W Mark, Hui, Jennie, Timens, Wim, Franceschini, Nora, Postma, Dirkje S, and Nickle, David C

Subjects
respiratory system, respiratory tract diseases
Abstract

Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs.

Published
2015
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29. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study (vol 9, e91621, 2014)

Author

Dijkstra, Akkelies E., Smolonska, Joanna, van den Berge, Maarten, Wijmenga, Ciska, Zanen, Pieter, Luinge, Marjan A., Platteel, Mathieu, Lammers, Jan-Willem, Dahlback, Magnus, Tosh, Kerrie, Hiemstra, Pieter S., Sterk, Peter J., Spira, Avi, Vestbo, Jorgen, Nordestgaard, Borge G., Benn, Marianne, Nielsen, Sune F., Dahl, Morten, Verschuren, W. Monique, Picavet, H. Susan J., Smit, Henriette A., Owsijewitsch, Michael, Kauczor, Hans U., de Koning, Harry J., Nizankowska-Mogilnicka, Eva, Mejza, Filip, Nastalek, Pawel, van Diemen, Cleo C., Cho, Michael H., Silverman, Edwin K., Crapo, James D., Beaty, Terri H., Lomas, David A., Bakke, Per, Gulsvik, Amund, Bossé, Yohan, Obeidat, Ma'en, Loth, Daan W., Lahousse, Lies, Rivadeneira, Fernando, Uitterlinden, Andre G., Hofman, Andre, Stricker, Bruno H., Brusselle, Guy G., van Duijn, Cornelia M., Brouwer, Uilke, Koppelman, Gerard H., Vonk, Judith M., Nawijn, Martijn C., Groen, Harry J. M., Timens, Wim, Boezen, H. Marike, Postma, Dirkje S., Amsterdam institute for Infection and Immunity, and Pulmonology

Abstract

[This corrects the article DOI: 10.1371/journal.pone.0091621.]

Published
2015

30. Integrative pathway genomics of lung function and airflow obstruction

Author

Lahousse, Lies, North, Kari E., Wilson, James F., Smith, Albert Vernon, Surakka, Ida, Wain, Louise V., Vitart, Veronique, Morrison, Alanna C., Gudnason, Vilmundur, Rawal, Rajesh, Alves, Alexessander C., Obeidat, Ma'en, Huffman, Jennifer E., Wilk, Jemma B., Zhao, Jing Hua, Brody, Jennifer A., Loth, Daan W., Ramasamy, Adaikalavan, Hancock, Dana B., Hofman, Albert, Tang, Wenbo, Evans, David M., Deary, Ian J., Strachan, David P., Hui, Jennie, Soler Artigas, María, Gharib, Sina A., Manichaikul, Ani, Birkland, Timothy P., Imboden, Medea, Gläser, Sven, and Boezen, H. Marike

Abstract

Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease.

Published
2015
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31. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Author

Chen, Lin, Tang, Wenbo, Kowgier, Matthew, Loth, Daan W., Joubert, Bonnie R., Hodge, Emily, Gharib, Sina A., Smith, Albert V., Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A., Harris, Tamara B., Hansel, Nadia N., Launer, Lenore J., Barnes, Kathleen C., Hansen, Joyanna G., Albrecht, Eva, Aldrich, Melinda C., Allerhand, Michael, Barr, R. Graham, Brusselle, Guy G., Couper, David J., Curjuric, Ivan, Davies, Gail, Deary, Ian J., Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Gu, Xiangjun, Hancock, Dana B., Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B., Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L., Meibohm, Bernd, Morris, Andrew P., Morrison, Alanna C., Musk, Bill, North, Kari E., Palmer, Lyle J., Probst-Hensch, Nicole M., Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome I., Schulz, Holger, Smith, Lewis J., Sood, Akshay, Starr, John M., Strachan, David P., Teumer, Alexander, Voorman, Arend, Wain, Louise V., Wells, Martin T., Wilk, Jemma B., Williams, O. Dale, Heckbert, Susan R., Stricker, Bruno H., London, Stephanie J., Fornage, Myriam, Tobin, Martin D., O?Connor, George T., Hall, Ian P., Cassano, Patricia A., and Chen, Lin

Abstract

Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 6 10-7). In addition, meta-analysis using the five cohorts with $3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18610-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Published
2014

32. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Loth, Daan W., Gharib, Sina A., Wain, Louise V., Franceschini, Nora, Koch, Beate, Pottinger, Tess D., Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P., James, Alan L., Huffman, Jennifer E., Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J., Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M., de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K., Fall, Tove, Launer, Lenore J., Loehr, Laura R., Fornage, Myriam, Li, Guo, Wilk, Jemma B., Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B., North, Kari E., Rudnicka, Alicja R., Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F., Hastie, Nicholas D., Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A., Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G., Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M., Wojczynski, Mary, Pouta, Anneli, Wild, Sarah H., Ingelsson, Erik, Rivadeneira, Fernando, Hysi, Pirro G., Eiriksdottir, Gudny, Morrison, Alanna C., Rotter, Jerome I., Gao, Wei, Postma, Dirkje S., White, Wendy B., Rich, Stephen S., Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J., Psaty, Bruce M., Lohman, Kurt, Burchard, Esteban G., Garcia, Melissa, Joubert, Bonnie R., McArdle, Wendy L., Musk, A Bill, Hansel, Nadia, Heckbert, Susan R., Zgaga, Lina, van Meurs, Joyce B.J., Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L., Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T., Ripatti, Samuli, Scott, Rodney J., Karrasch, Stefan, Grallert, Harald, Gaddis, Nathan C., Starr, John M., Wijmenga, Cisca, Minster, Ryan L., Lederer, David J., Pekkanen, Juha, Gyllensten, Ulf, Campbell, Harry, Morris, Andrew P., Hammond, Christopher J., Burkart, Kristin M, Beilby, John, Kritchevsky, Stephen B., Gudnason, Vilmundur, Hancock, Dana B., Williams, O Dale, Polasek, Ozren, Zemunik, Tatijana, Kolcic, Ivana, Petrini, Marcy F., Wjst, Matthias, Kim, Woo Jin, Porteous, David J., Smith, Blair H., Viljanen, Anne, Attia, John R., Sayers, Ian, Hampel, Regina, Gieger, Christian, Deary, Ian J, Boezen, H. Marike, Newman, Anne, Jarvelin, Marjo-Riitta, Wilson, James F, Lind, Lars, Stricker, Bruno H., Teumer, Alexander, Spector, Timothy D., Peters, Marjolein J., Lange, Leslie A., Barr, R. Graham, Bracke, Ken R., Verhamme, Fien M., Sung, Joohon, Hiemstra, Pieter S., Cassano, Patricia A., Sood, Akshay, Hayward, Caroline, Hall, Ian P., Brusselle, Guy G., Tobin, Martin D., and London, Stephanie J.

Subjects
respiratory system, Genetics research, Genome-wide association studies, Population genetics, Respiratory tract diseases, respiratory tract diseases
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.© 2014 Nature America, Inc. All rights reserved.

Published
2014

33. β-Adrenoceptor blockers and pulmonary function in the general population: the Rotterdam Study

Author

Loth, Daan W, Brusselle, Guy G, Lahousse, Lies, Hofman, Albert, Leufkens, Hubert G M, Stricker, Bruno H, Sub Pharmacoepidemiology, and Pharmacoepidemiology and Clinical Pharmacology

Subjects
Aged, 80 and over, Cohort Studies, Male, Forced Expiratory Volume, Adrenergic beta-Antagonists, Vital Capacity, Humans, Female, Middle Aged, Aged
Abstract

AIM: β-Adrenoceptor blockers have been used with caution in patients with obstructive lung diseases such as asthma or chronic obstructive pulmonary disease (COPD), due to the potentially increased airway reactivity and risk of bronchial obstruction. Cardioselective β-adrenoceptor blockers have a more beneficial profile than non-cardioselective β-adrenoceptor blockers and can be safely prescribed to patients with both cardiovascular disease and COPD. We hypothesized that cardioselective β-adrenoceptor blockers also affect pulmonary function. METHODS: This study was performed within the Rotterdam Study, a prospective population-based cohort study. Effects of cardioselective and non-cardioselective β-adrenoceptor blockers on pulmonary function were analysed using regression techniques with multivariable adjustment for potential confounders. RESULTS: Current use of non-cardioselective β-adrenoceptor blockers was significantly associated with a lower forced expiratory volume in 1 s (FEV1) of -198 ml (95% CI -301, -96), with a lower forced vital capacity (FVC) of -223 ml (95% CI -367, -79) and with a decreased FEV1 : FVC of -1.38% (95% CI -2.74, -0.13%). Current use of cardioselective β-adrenoceptor blockers was significantly associated with a lower FEV1 of -118 ml (95% CI -157, -78) and with a lower FVC of -167 ml (95% CI -222, -111), but did not affect FEV1: FVC. After exclusion of patients with COPD, asthma and heart failure the effects of cardioselective β-adrenoceptor blockers remained significant for FEV1 (-142 ml [95% CI -189, -96]) and for FVC (-176 ml [95% CI -236, -117]). CONCLUSION: In our study both non-cardioselective and cardioselective β-adrenoceptor blockers had a clinically relevant effect on both FEV1 and FVC. In contrast to cardioselective β-adrenoceptor blockers, use of non-cardioselective β-adrenoceptor blockers was associated with a significantly lower FEV1: FVC.

Published
2014

34. Correction: Susceptibility to chronic mucus hypersecretion, a genome wide association study

Author

Cardiometabolic Health, Circulatory Health, Child Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Longziekten, Infection & Immunity, Public Health Epidemiologie, Dijkstra, Akkelies E., Smolonska, Joanna, Van Den Berge, Maarten, Wijmenga, Ciska, Zanen, Pieter, Luinge, Marjan A., Platteel, Mathieu, Lammers, Jan Willem, Dahlback, Magnus, Tosh, Kerrie, Hiemstra, Pieter S., Sterk, Peter J., Spira, Avi, Vestbo, Jorgen, Nordestgaard, Borge G., Benn, Marianne, Nielsen, Sune F., Dahl, Morten, Verschuren, W. Monique, Picavet, H. Susan J, Smit, Henriette A., Owsijewitsch, Michael, Kauczor, Hans U., De Koning, Harry J., Nizankowska-Mogilnicka, Eva, Mejza, Filip, Nastalek, Pawel, Van Diemen, Cleo C., Cho, Michael H., Silverman, Edwin K., Crapo, James D., Beaty, Terri H., Lomas, David A., Bakke, Per, Gulsvik, Amund, Bossé, Yohan, Obeidat, Ma'en, Loth, Daan W., Lahousse, Lies, Rivadeneira, Fernando, Uitterlinden, Andre G., Hofman, Andre, Stricker, Bruno H., Brusselle, Guy G., Van Duijn, Cornelia M., Brouwer, Uilke, Koppelman, Gerard H., Vonk, Judith M., Nawijn, Martijn C., Groen, Harry J M, Timens, Wim, Boezen, H. Marike, Postma, Dirkje S., Cardiometabolic Health, Circulatory Health, Child Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Longziekten, Infection & Immunity, Public Health Epidemiologie, Dijkstra, Akkelies E., Smolonska, Joanna, Van Den Berge, Maarten, Wijmenga, Ciska, Zanen, Pieter, Luinge, Marjan A., Platteel, Mathieu, Lammers, Jan Willem, Dahlback, Magnus, Tosh, Kerrie, Hiemstra, Pieter S., Sterk, Peter J., Spira, Avi, Vestbo, Jorgen, Nordestgaard, Borge G., Benn, Marianne, Nielsen, Sune F., Dahl, Morten, Verschuren, W. Monique, Picavet, H. Susan J, Smit, Henriette A., Owsijewitsch, Michael, Kauczor, Hans U., De Koning, Harry J., Nizankowska-Mogilnicka, Eva, Mejza, Filip, Nastalek, Pawel, Van Diemen, Cleo C., Cho, Michael H., Silverman, Edwin K., Crapo, James D., Beaty, Terri H., Lomas, David A., Bakke, Per, Gulsvik, Amund, Bossé, Yohan, Obeidat, Ma'en, Loth, Daan W., Lahousse, Lies, Rivadeneira, Fernando, Uitterlinden, Andre G., Hofman, Andre, Stricker, Bruno H., Brusselle, Guy G., Van Duijn, Cornelia M., Brouwer, Uilke, Koppelman, Gerard H., Vonk, Judith M., Nawijn, Martijn C., Groen, Harry J M, Timens, Wim, Boezen, H. Marike, and Postma, Dirkje S.

Published
2015

35. Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function

Author

Sood, Akshay, Liu, Jason Z., Smolonska, Joanna, Burkart, Kristin M., Elliott, Paul, Manning, Alisa K., Imboden, Medea, Homuth, Georg, Loth, Daan W., Eijgelsheim, Mark, Zhao, Jing Hua, Aschard, Hugues, Janson, Christer, Smith, Albert V., Lohman, Kurt, Artigas, María Soler, Gu, Xiangjun, Tang, Wenbo, Zhai, Guangju, Hysi, Pirro G., Curjuric, Ivan, Wilk, Jemma B., Loos, Ruth J. F., Koch, Beate, McArdle, Wendy L., Harris, Tamara B., Henry, Amanda, Loehr, Laura R., Gharib, Sina A., Manichaikul, Ani, Hancock, Dana B., and Ramasamy, Adaikalavan

Subjects
respiratory system, respiratory tract diseases
Abstract

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Published
2012
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36. Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

Author

Franceschini, Nora, Bentley, Amy R., Lopez, Lorna M., Gulsvik, Amund, Curjuric, Ivan, Harris, Tamara B., Manichaikul, Ani, Loehr, Laura R., Loth, Daan W., Shrine, Nick R. G., Cho, Michael H., Bakke, Per, Wilk, Jemma B., Davies, Gail, Tang, Wenbo, Heckbert, Susan R., Chen, Ting-hsu, Beaty, Terri H., Crapo, James D., Aldrich, Melinda, Henry, Amanda P., Zhao, Jing Hua, Borecki, Ingrid B., Couper, David, Latourelle, Jeanne C., Brusselle, Guy G., Smith, Albert Vernon, Hui, Jennie, Dupuis, Josée, Burkart, Kristin M., Hancock, Dana B., and Smolonska, Joanna

Subjects
respiratory tract diseases
Abstract

Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.

Published
2012
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37. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Author

Soler Artigas, María, Loth, Daan W, Wain, Louise V, Gharib, Sina A, Obeidat, Ma'en, Tang, Wenbo, Zhai, Guangju, Zhao, Jing Hua, Smith, Albert Vernon, Huffman, Jennifer E, Albrecht, Eva, Jackson, Catherine M, Evans, David M, Cadby, Gemma, Fornage, Myriam, Manichaikul, Ani, Lopez, Lorna M, Johnson, Toby, Aldrich, Melinda C, Aspelund, Thor, Barroso, Inês, Campbell, Harry, Cassano, Patricia A, Couper, David J, Eiriksdottir, Gudny, Franceschini, Nora, Garcia, Melissa, Gieger, Christian, Gislason, Gauti Kjartan, Grkovic, Ivica, Hammond, Christopher J, Hancock, Dana B, Harris, Tamara B, Ramasamy, Adaikalavan, Heckbert, Susan R, Heliövaara, Markku, Homuth, Georg, Hysi, Pirro G, James, Alan L, Jankovic, Stipan, Joubert, Bonnie R, Karrasch, Stefan, Klopp, Norman, Koch, Beate, Kritchevsky, Stephen B, Launer, Lenore J, Liu, Yongmei, Loehr, Laura R, Lohman, Kurt, Loos, Ruth JF, Lumley, Thomas, Al Balushi, Khalid A, Ang, Wei Q, Barr, R Graham, Beilby, John, Blakey, John D, Boban, Mladen, Boraska, Vesna, Brisman, Jonas, Britton, John R, Brusselle, Guy G, Cooper, Cyrus, Curjuric, Ivan, Dahgam, Santosh, Deary, Ian J, Ebrahim, Shah, Eijgelsheim, Mark, Francks, Clyde, Gaysina, Darya, Granell, Raquel, Gu, Xiangjun, Hankinson, John L, Hardy, Rebecca, Harris, Sarah E, Henderson, John, Henry, Amanda, Hingorani, Aroon D, Hofman, Albert, Holt, Patrick G, Hui, Jennie, Hunter, Michael L, Imboden, Medea, Jameson, Karen A, Kerr, Shona M, Kolcic, Ivana, Kronenberg, Florian, Liu, Jason Z, Marchini, Jonathan, McKeever, Tricia, Morris, Andrew D, Olin, Anna-Carin, Porteous, David J, Postma, Dirkje S, Rich, Stephen S, Ring, Susan M, Rivadeneira, Fernando, Rochat, Thierry, Sayer, Avan Aihie, Sayers, Ian, Sly, Peter D, Smith, George Davey, Sood, Akshay, Starr, John M, Uitterlinden, André G, Vonk, Judith M, Wannamethee, S Goya, Whincup, Peter H, Wijmenga, Cisca, Williams, O Dale, Wong, Andrew, Mangino, Massimo, Marciante, Kristin D, McArdle, Wendy L, Meibohm, Bernd, Morrison, Alanna C, North, Kari E, Omenaas, Ernst, Palmer, Lyle J, Pietiläinen, Kirsi H, Pin, Isabelle, Pola Sbreve Ek, Ozren, Pouta, Anneli, Psaty, Bruce M, Hartikainen, Anna-Liisa, Rantanen, Taina, Ripatti, Samuli, Rotter, Jerome I, Rudan, Igor, Rudnicka, Alicja R, Schulz, Holger, Shin, So-Youn, Spector, Tim D, Surakka, Ida, Vitart, Veronique, Völzke, Henry, Wareham, Nicholas J, Warrington, Nicole M, Wichmann, H-Erich, Wild, Sarah H, Wilk, Jemma B, Wjst, Matthias, Wright, Alan F, Zgaga, Lina, Zemunik, Tatijana, Pennell, Craig E, Nyberg, Fredrik, Kuh, Diana, Holloway, John W, Boezen, H Marike, Lawlor, Debbie A, Morris, Richard W, Probst-Hensch, Nicole, International Lung Cancer Consortium, GIANT consortium, Kaprio, Jaakko, Wilson, James F, Hayward, Caroline, Kähönen, Mika, Heinrich, Joachim, Musk, Arthur W, Jarvis, Deborah L, Gläser, Sven, Järvelin, Marjo-Riitta, Ch Stricker, Bruno H, Elliott, Paul, O'Connor, George T, Strachan, David P, London, Stephanie J, Hall, Ian P, Gudnason, Vilmundur, and Tobin, Martin D

Abstract

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Published
2011

38. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Author

Smith, Albert Vernon, Cassano, Patricia A, Zhao, Jing Hua, Eiriksdottir, Gudny, Gislason, Gauti Kjartan, Huffman, Jennifer E, Manichaikul, Ani, Garcia, Melissa, Obeidat, Ma'en, Jackson, Catherine M, Franceschini, Nora, Gieger, Christian, Grkovic, Ivica, Lopez, Lorna M, Wain, Louise V, Albrecht, Eva, Gharib, Sina A, Loth, Daan W, Hancock, Dana B, Aldrich, Melinda C, Hammond, Christopher J, Evans, David M, Zhai, Guangju, Cadby, Gemma, Aspelund, Thor, Artigas, María Soler, Fornage, Myriam, Barroso, Inês, Johnson, Toby, Tang, Wenbo, Campbell, Harry, and Couper, David J

Abstract

Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P

Published
2011
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39. Prevalence of Pulmonary Hypertension in the General Population: The Rotterdam Study

Author

Moreira, Eduardo M., primary, Gall, Henning, additional, Leening, Maarten J. G., additional, Lahousse, Lies, additional, Loth, Daan W., additional, Krijthe, Bouwe P., additional, Kiefte-de Jong, Jessica C., additional, Brusselle, Guy G., additional, Hofman, Albert, additional, Stricker, Bruno H., additional, Ghofrani, Hossein A., additional, Franco, Oscar H., additional, and Felix, Janine F., additional

Published
2015
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40. Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis

Author

Smolonska, Joanna, Koppelman, Gerard H., Wijmenga, Cisca, Vonk, Judith M., Zanen, Pieter, Bruinenberg, Marcel, Curjuric, Ivan, Imboden, Medea, Thun, Gian-Andri, Franke, Lude, Probst-Hensch, Nicole M., Nuernberg, Peter, Riemersma, Roland A., van Schayck, Constant P., Loth, Daan W., Brusselle, Guy G., Stricker, Bruno H., Hofman, Albert, Uitterlinden, Andre G., Lahousse, Lies, London, Stephanie J., Loehr, Laura R., Manichaikul, Ani, Barr, R. Graham, Donohue, Kathleen M., Rich, Stephen S., Pare, Peter, Bosse, Yohan, Hao, Ke, van den Berge, Maarten, Groen, Harry J. M., Lammers, Jan-Willem J., Mali, Willem, Boezen, H. Marike, Postma, Dirkje S., Smolonska, Joanna, Koppelman, Gerard H., Wijmenga, Cisca, Vonk, Judith M., Zanen, Pieter, Bruinenberg, Marcel, Curjuric, Ivan, Imboden, Medea, Thun, Gian-Andri, Franke, Lude, Probst-Hensch, Nicole M., Nuernberg, Peter, Riemersma, Roland A., van Schayck, Constant P., Loth, Daan W., Brusselle, Guy G., Stricker, Bruno H., Hofman, Albert, Uitterlinden, Andre G., Lahousse, Lies, London, Stephanie J., Loehr, Laura R., Manichaikul, Ani, Barr, R. Graham, Donohue, Kathleen M., Rich, Stephen S., Pare, Peter, Bosse, Yohan, Hao, Ke, van den Berge, Maarten, Groen, Harry J. M., Lammers, Jan-Willem J., Mali, Willem, Boezen, H. Marike, and Postma, Dirkje S.

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background (Dutch hypothesis). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chrl3q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) kappa beta pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p=9.96 x 10(-9)). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression. Inflammatory processes differ in asthma and COPD and are mediated by NF-kappa beta, which could be driven by the same underlying genes, COMMD10 and DDX1. None of the SNPs reached genome-wide significance. Our eQTL studies support a functional role for two COMMD10 SNPs, since they influence gene expression in both blood cells and lung tissue. Our findings suggest that there is either no common genetic component in asthma and COPD or, alternatively, different environmental factors, e.g. lifestyle and occupation in different countries and continents, which may have obscured the genetic common contribution.

Published
2014

41. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

Author

Dijkstra, Akkelies E, Smolonska, Joanna, van den Berge, Maarten, Wijmenga, Ciska, Zanen, Pieter, Luinge, Marjan A, Platteel, Mathieu, Lammers, Jan-Willem, Dahlback, Magnus, Tosh, Kerrie, Hiemstra, Pieter S, Sterk, Peter J, Spira, Avi, Vestbo, Jorgen, Nordestgaard, Børge, Benn, Marianne, Nielsen, Sune F, Dahl, Morten, Verschuren, W Monique, Picavet, H Susan J, Smit, Henriette A, Owsijewitsch, Michael, Kauczor, Hans U, de Koning, Harry J, Nizankowska-Mogilnicka, Eva, Mejza, Filip, Nastalek, Pawel, van Diemen, Cleo C, Cho, Michael H, Silverman, Edwin K, Crapo, James D, Beaty, Terri H, Lomas, David A, Bakke, Per, Gulsvik, Amund, Bossé, Yohan, Obeidat, M A, Loth, Daan W, Lahousse, Lies, Rivadeneira, Fernando, Uitterlinden, Andre G, Hofman, Andre, Stricker, Bruno H, Brusselle, Guy G, van Duijn, Cornelia M, Brouwer, Uilke, Koppelman, Gerard H, Vonk, Judith M, Nawijn, Martijn C, Groen, Harry J M, Dijkstra, Akkelies E, Smolonska, Joanna, van den Berge, Maarten, Wijmenga, Ciska, Zanen, Pieter, Luinge, Marjan A, Platteel, Mathieu, Lammers, Jan-Willem, Dahlback, Magnus, Tosh, Kerrie, Hiemstra, Pieter S, Sterk, Peter J, Spira, Avi, Vestbo, Jorgen, Nordestgaard, Børge, Benn, Marianne, Nielsen, Sune F, Dahl, Morten, Verschuren, W Monique, Picavet, H Susan J, Smit, Henriette A, Owsijewitsch, Michael, Kauczor, Hans U, de Koning, Harry J, Nizankowska-Mogilnicka, Eva, Mejza, Filip, Nastalek, Pawel, van Diemen, Cleo C, Cho, Michael H, Silverman, Edwin K, Crapo, James D, Beaty, Terri H, Lomas, David A, Bakke, Per, Gulsvik, Amund, Bossé, Yohan, Obeidat, M A, Loth, Daan W, Lahousse, Lies, Rivadeneira, Fernando, Uitterlinden, Andre G, Hofman, Andre, Stricker, Bruno H, Brusselle, Guy G, van Duijn, Cornelia M, Brouwer, Uilke, Koppelman, Gerard H, Vonk, Judith M, Nawijn, Martijn C, and Groen, Harry J M

Abstract

BACKGROUND: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10(-9)) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.CONCLUSIONS: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

Published
2014

42. Interferon gamma receptor 2 gene variants are associated with liver fibrosis in the general population: the Rotterdam Study

Author

Plompen, Elisabeth P C, primary, Hansen, Bettina E, additional, Schouten, Jeoffrey N L, additional, Darwish Murad, Sarwa, additional, Loth, Daan W, additional, Brouwer, Willem Pieter, additional, Isaacs, Aaron, additional, Taimr, Pavel, additional, Hofman, Albert, additional, van Duijn, Cornelia M, additional, Uitterlinden, André G, additional, C Stricker, Bruno H, additional, Leebeek, Frank W G, additional, and Janssen, Harry L A, additional

Published
2014
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43. Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis

Author

Smolonska, Joanna, primary, Koppelman, Gerard H., additional, Wijmenga, Cisca, additional, Vonk, Judith M., additional, Zanen, Pieter, additional, Bruinenberg, Marcel, additional, Curjuric, Ivan, additional, Imboden, Medea, additional, Thun, Gian-Andri, additional, Franke, Lude, additional, Probst-Hensch, Nicole M., additional, Nürnberg, Peter, additional, Riemersma, Roland A., additional, van Schayck, Constant P., additional, Loth, Daan W., additional, Brusselle, Guy G., additional, Stricker, Bruno H., additional, Hofman, Albert, additional, Uitterlinden, André G., additional, Lahousse, Lies, additional, London, Stephanie J., additional, Loehr, Laura R., additional, Manichaikul, Ani, additional, Barr, R. Graham, additional, Donohue, Kathleen M., additional, Rich, Stephen S., additional, Pare, Peter, additional, Bossé, Yohan, additional, Hao, Ke, additional, van den Berge, Maarten, additional, Groen, Harry J.M., additional, Lammers, Jan-Willem J., additional, Mali, Willem, additional, Boezen, H. Marike, additional, and Postma, Dirkje S., additional

Published
2014
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45. Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function

Author

Hancock, Dana B, Artigas, María Soler, Gharib, Sina A, Henry, Amanda, Manichaikul, Ani, Ramasamy, Adaikalavan, Loth, Daan W, Imboden, Medea, Koch, Beate, McArdle, Wendy L, Smith, Albert V, Smolonska, Joanna, Sood, Akshay, Tang, Wenbo, Wilk, Jemma B, Zhai, Guangju, Zhao, Jing Hua, Aschard, Hugues, Burkart, Kristin M, Curjuric, Ivan, Eijgelsheim, Mark, Elliott, Paul, Gu, Xiangjun, Harris, Tamara B, Janson, Christer, Homuth, Georg, Hysi, Pirro G, Liu, Jason Z, Loehr, Laura R, Lohman, Kurt, Loos, Ruth J F, Manning, Alisa K, Marciante, Kristin D, Obeidat, Ma'en, Postma, Dirkje S, Aldrich, Melinda C, Brusselle, Guy G, Chen, Ting-Hsu, Eiriksdottir, Gudny, Franceschini, Nora, Heinrich, Joachim, Rotter, Jerome I, Wijmenga, Cisca, Williams, O Dale, Bentley, Amy R, Hofman, Albert, Laurie, Cathy C, Lumley, Thomas, Morrison, Alanna C, Joubert, Bonnie R, Rivadeneira, Fernando, Couper, David J, Kritchevsky, Stephen B, Liu, Yongmei, Wjst, Matthias, Wain, Louise V, Vonk, Judith M, Uitterlinden, André G, Rochat, Thierry, Rich, Stephen S, Psaty, Bruce M, O'Connor, George T, North, Kari E, Mirel, Daniel B, Meibohm, Bernd, Launer, Lenore J, Khaw, Kay-Tee, Hartikainen, Anna-Liisa, Hammond, Christopher J, Gläser, Sven, Marchini, Jonathan, Kraft, Peter, Wareham, Nicholas J, Völzke, Henry, Stricker, Bruno H C, Spector, Timothy D, Probst-Hensch, Nicole M, Jarvis, Deborah, Jarvelin, Marjo-Riitta, Heckbert, Susan R, Gudnason, Vilmundur, Boezen, H Marike, Barr, R Graham, Cassano, Patricia A, Strachan, David P, Fornage, Myriam, Hall, Ian P, Dupuis, Josée, Tobin, Martin D, London, Stephanie J, Hancock, Dana B, Artigas, María Soler, Gharib, Sina A, Henry, Amanda, Manichaikul, Ani, Ramasamy, Adaikalavan, Loth, Daan W, Imboden, Medea, Koch, Beate, McArdle, Wendy L, Smith, Albert V, Smolonska, Joanna, Sood, Akshay, Tang, Wenbo, Wilk, Jemma B, Zhai, Guangju, Zhao, Jing Hua, Aschard, Hugues, Burkart, Kristin M, Curjuric, Ivan, Eijgelsheim, Mark, Elliott, Paul, Gu, Xiangjun, Harris, Tamara B, Janson, Christer, Homuth, Georg, Hysi, Pirro G, Liu, Jason Z, Loehr, Laura R, Lohman, Kurt, Loos, Ruth J F, Manning, Alisa K, Marciante, Kristin D, Obeidat, Ma'en, Postma, Dirkje S, Aldrich, Melinda C, Brusselle, Guy G, Chen, Ting-Hsu, Eiriksdottir, Gudny, Franceschini, Nora, Heinrich, Joachim, Rotter, Jerome I, Wijmenga, Cisca, Williams, O Dale, Bentley, Amy R, Hofman, Albert, Laurie, Cathy C, Lumley, Thomas, Morrison, Alanna C, Joubert, Bonnie R, Rivadeneira, Fernando, Couper, David J, Kritchevsky, Stephen B, Liu, Yongmei, Wjst, Matthias, Wain, Louise V, Vonk, Judith M, Uitterlinden, André G, Rochat, Thierry, Rich, Stephen S, Psaty, Bruce M, O'Connor, George T, North, Kari E, Mirel, Daniel B, Meibohm, Bernd, Launer, Lenore J, Khaw, Kay-Tee, Hartikainen, Anna-Liisa, Hammond, Christopher J, Gläser, Sven, Marchini, Jonathan, Kraft, Peter, Wareham, Nicholas J, Völzke, Henry, Stricker, Bruno H C, Spector, Timothy D, Probst-Hensch, Nicole M, Jarvis, Deborah, Jarvelin, Marjo-Riitta, Heckbert, Susan R, Gudnason, Vilmundur, Boezen, H Marike, Barr, R Graham, Cassano, Patricia A, Strachan, David P, Fornage, Myriam, Hall, Ian P, Dupuis, Josée, Tobin, Martin D, and London, Stephanie J

Abstract

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Published
2012
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47. A Genome-Wide Association Study for Venous Thromboembolism: The Extended Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Author

Tang, Weihong, primary, Teichert, Martina, additional, Chasman, Daniel I., additional, Heit, John A., additional, Morange, Pierre-Emmanuel, additional, Li, Guo, additional, Pankratz, Nathan, additional, Leebeek, Frank W., additional, Paré, Guillaume, additional, de Andrade, Mariza, additional, Tzourio, Christophe, additional, Psaty, Bruce M., additional, Basu, Saonli, additional, Ruiter, Rikje, additional, Rose, Lynda, additional, Armasu, Sebastian M., additional, Lumley, Thomas, additional, Heckbert, Susan R., additional, Uitterlinden, André G., additional, Lathrop, Mark, additional, Rice, Kenneth M., additional, Cushman, Mary, additional, Hofman, Albert, additional, Lambert, Jean-Charles, additional, Glazer, Nicole L., additional, Pankow, James S., additional, Witteman, Jacqueline C., additional, Amouyel, Philippe, additional, Bis, Joshua C., additional, Bovill, Edwin G., additional, Kong, Xiaoxiao, additional, Tracy, Russell P., additional, Boerwinkle, Eric, additional, Rotter, Jerome I., additional, Trégouët, David-Alexandre, additional, Loth, Daan W., additional, Stricker, Bruno H. Ch., additional, Ridker, Paul M., additional, Folsom, Aaron R., additional, and Smith, Nicholas L., additional

Published
2013
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48. Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function

Author

Hancock, Dana B., primary, Artigas, María Soler, additional, Gharib, Sina A., additional, Henry, Amanda, additional, Manichaikul, Ani, additional, Ramasamy, Adaikalavan, additional, Loth, Daan W., additional, Imboden, Medea, additional, Koch, Beate, additional, McArdle, Wendy L., additional, Smith, Albert V., additional, Smolonska, Joanna, additional, Sood, Akshay, additional, Tang, Wenbo, additional, Wilk, Jemma B., additional, Zhai, Guangju, additional, Zhao, Jing Hua, additional, Aschard, Hugues, additional, Burkart, Kristin M., additional, Curjuric, Ivan, additional, Eijgelsheim, Mark, additional, Elliott, Paul, additional, Gu, Xiangjun, additional, Harris, Tamara B., additional, Janson, Christer, additional, Homuth, Georg, additional, Hysi, Pirro G., additional, Liu, Jason Z., additional, Loehr, Laura R., additional, Lohman, Kurt, additional, Loos, Ruth J. F., additional, Manning, Alisa K., additional, Marciante, Kristin D., additional, Obeidat, Ma'en, additional, Postma, Dirkje S., additional, Aldrich, Melinda C., additional, Brusselle, Guy G., additional, Chen, Ting-hsu, additional, Eiriksdottir, Gudny, additional, Franceschini, Nora, additional, Heinrich, Joachim, additional, Rotter, Jerome I., additional, Wijmenga, Cisca, additional, Williams, O. Dale, additional, Bentley, Amy R., additional, Hofman, Albert, additional, Laurie, Cathy C., additional, Lumley, Thomas, additional, Morrison, Alanna C., additional, Joubert, Bonnie R., additional, Rivadeneira, Fernando, additional, Couper, David J., additional, Kritchevsky, Stephen B., additional, Liu, Yongmei, additional, Wjst, Matthias, additional, Wain, Louise V., additional, Vonk, Judith M., additional, Uitterlinden, André G., additional, Rochat, Thierry, additional, Rich, Stephen S., additional, Psaty, Bruce M., additional, O'Connor, George T., additional, North, Kari E., additional, Mirel, Daniel B., additional, Meibohm, Bernd, additional, Launer, Lenore J., additional, Khaw, Kay-Tee, additional, Hartikainen, Anna-Liisa, additional, Hammond, Christopher J., additional, Gläser, Sven, additional, Marchini, Jonathan, additional, Kraft, Peter, additional, Wareham, Nicholas J., additional, Völzke, Henry, additional, Stricker, Bruno H. C., additional, Spector, Timothy D., additional, Probst-Hensch, Nicole M., additional, Jarvis, Deborah, additional, Jarvelin, Marjo-Riitta, additional, Heckbert, Susan R., additional, Gudnason, Vilmundur, additional, Boezen, H. Marike, additional, Barr, R. Graham, additional, Cassano, Patricia A., additional, Strachan, David P., additional, Fornage, Myriam, additional, Hall, Ian P., additional, Dupuis, Josée, additional, Tobin, Martin D., additional, and London, Stephanie J., additional

Published
2012
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