Search

Your search keyword '"Jackson, Victoria E."' showing total 245 results
Start Over Author "Jackson, Victoria E."
245 results on '"Jackson, Victoria E."'

2. Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Shrine, Nick, Guyatt, Anna L., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Hobbs, Brian D., Melbourne, Carl A., Batini, Chiara, Fawcett, Katherine A., Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F., Obeidat, Ma’en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Sun, Benjamin B., Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E., Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J., Bakke, Per S., Beaty, Terri H., Bleecker, Eugene R., Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D., Danesh, John, DeMeo, Dawn L., Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L., Hao, Ke, Hoffman, Joshua D., Hokanson, John E., Homuth, Georg, Joshi, Peter K., Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian’an, Mahajan, Anubha, Maranville, Joseph C., Murray, Alison, Nickle, David C., Packer, Richard, Parker, Margaret M., Paynton, Megan L., Porteous, David J., Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Sin, Don D., Smith, Blair H., Artigas, María Soler, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul R. H. J., Van den Berge, Maarten, Whittaker, John C., Woodruff, Prescott G., Yerges-Armstrong, Laura M., Troyanskaya, Olga G., Raitakari, Olli T., Kähönen, Mika, Polašek, 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, Silverman, Edwin K., Hayward, Caroline, Morris, Andrew P., Butterworth, Adam S., Scott, Robert A., Walters, Robin G., Meyers, Deborah A., Cho, Michael H., Strachan, David P., Hall, Ian P., Tobin, Martin D., and Wain, Louise V.

Published
2024
Full Text
View/download PDF

3. Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources

Author

Braat, Sabine, Fielding, Katherine L, Han, Jiru, Jackson, Victoria E, Zaloumis, Sophie, Xu, Jessica Xu Hui, Moir-Meyer, Gemma, Blaauwendraad, Sophia M, Jaddoe, Vincent W V, Gaillard, Romy, Parkin, Patricia C, Borkhoff, Cornelia M, Keown-Stoneman, Charles D G, Birken, Catherine S, Maguire, Jonathon L, Bahlo, Melanie, Davidson, Eliza M, and Pasricha, Sant-Rayn

Published
2024
Full Text
View/download PDF

4. A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation

Author

Garnish, Sarah E., Martin, Katherine R., Kauppi, Maria, Jackson, Victoria E., Ambrose, Rebecca, Eng, Vik Ven, Chiou, Shene, Meng, Yanxiang, Frank, Daniel, Tovey Crutchfield, Emma C., Patel, Komal M., Jacobsen, Annette V., Atkin-Smith, Georgia K., Di Rago, Ladina, Doerflinger, Marcel, Horne, Christopher R., Hall, Cathrine, Young, Samuel N., Cook, Matthew, Athanasopoulos, Vicki, Vinuesa, Carola G., Lawlor, Kate E., Wicks, Ian P., Ebert, Gregor, Ng, Ashley P., Slade, Charlotte A., Pearson, Jaclyn S., Samson, André L., Silke, John, Murphy, James M., and Hildebrand, Joanne M.

Published
2023
Full Text
View/download PDF

5. Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

Author

Kaspi, Antony, Hildebrand, Michael S., Jackson, Victoria E., Braden, Ruth, van Reyk, Olivia, Howell, Tegan, Debono, Simone, Lauretta, Mariana, Morison, Lottie, Coleman, Matthew J., Webster, Richard, Coman, David, Goel, Himanshu, Wallis, Mathew, Dabscheck, Gabriel, Downie, Lilian, Baker, Emma K., Parry-Fielder, Bronwyn, Ballard, Kirrie, Harrold, Eva, Ziegenfusz, Shaun, Bennett, Mark F., Robertson, Erandee, Wang, Longfei, Boys, Amber, Fisher, Simon E., Amor, David J., Scheffer, Ingrid E., Bahlo, Melanie, and Morgan, Angela T.

Published
2023
Full Text
View/download PDF

6. Iron homeostasis governs erythroid phenotype in polycythemia vera

Author

Bennett, Cavan, Jackson, Victoria E., Pettikiriarachchi, Anne, Hayman, Thomas, Schaeper, Ute, Moir-Meyer, Gemma, Fielding, Katherine, Ataide, Ricardo, Clucas, Danielle, Baldi, Andrew, Garnham, Alexandra L., Li-Wai-Suen, Connie S. N., Loughran, Stephen J., Baxter, E. Joanna, Green, Anthony R., Alexander, Warren S., Bahlo, Melanie, Burbury, Kate, Ng, Ashley P., and Pasricha, Sant-Rayn

Published
2023
Full Text
View/download PDF

7. Correction: Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

Author

Kaspi, Antony, Hildebrand, Michael S., Jackson, Victoria E., Braden, Ruth, van Reyk, Olivia, Howell, Tegan, Debono, Simone, Lauretta, Mariana, Morison, Lottie, Coleman, Matthew J., Webster, Richard, Coman, David, Goel, Himanshu, Wallis, Mathew, Dabscheck, Gabriel, Downie, Lilian, Baker, Emma K., Parry-Fielder, Bronwyn, Ballard, Kirrie, Harrold, Eva, Ziegenfusz, Shaun, Bennett, Mark F., Robertson, Erandee, Wang, Longfei, Boys, Amber, Fisher, Simon E., Amor, David J., Scheffer, Ingrid E., Bahlo, Melanie, and Morgan, Angela T.

Published
2023
Full Text
View/download PDF

9. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Author

Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, and Gharib, Sina A

Subjects
Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

Published
2018

10. 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

11. Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Author

Soler Artigas, María, Jackson, Victoria E, Strachan, David P, Hui, Jennie, James, Alan L, Kerr, Shona M, Polasek, Ozren, Vitart, Veronique, Marten, Jonathan, Rudan, Igor, Kähönen, Mika, Surakka, Ida, Gieger, Christian, Karrasch, Stefan, Rawal, Rajesh, Schulz, Holger, Deary, Ian J, Harris, Sarah E, Enroth, Stefan, Gyllensten, Ulf, Imboden, Medea, Probst-Hensch, Nicole M, Lehtimäki, Terho, Raitakari, Olli T, Langenberg, Claudia, Luan, Jian'an, Wareham, Nick, Zhao, Jing Hua, Hayward, Caroline, Murray, Alison, Porteous, David J, Smith, Blair H, Jarvelin, Marjo-Riitta, Wielscher, Matthias, Joshi, Peter K, Kentistou, Katherine A, Timmers, Paul RHJ, Wilson, James F, Cook, James P, Lind, Lars, Mahajan, Anubha, Morris, Andrew P, Ewert, Ralf, Homuth, Georg, Stubbe, Beate, Weiss, Stefan, Zeggini, Eleftheria, Moll, Matthew, Sakornsakolpat, Phuwanat, Shrine, Nick, Hobbs, Brian D, DeMeo, Dawn L, John, Catherine, Guyatt, Anna L, McGeachie, Michael J, Gharib, Sina A, Obeidat, Ma'en, Lahousse, Lies, Wijnant, Sara R A, Brusselle, Guy, Meyers, Deborah A, Bleecker, Eugene R, Li, Xingnan, Tal-Singer, Ruth, Manichaikul, Ani, Rich, Stephen S, Won, Sungho, Kim, Woo Jin, Do, Ah Ra, Washko, George R, Barr, R Graham, Psaty, Bruce M, Bartz, Traci M, Hansel, Nadia N, Barnes, Kathleen, Hokanson, John E, Crapo, James D, Lynch, David, Bakke, Per, Gulsvik, Amund, Hall, Ian P, Wain, Louise, Weiss, Scott T, Silverman, Edwin K, Dudbridge, Frank, Tobin, Martin D, and Cho, Michael H

Published
2020
Full Text
View/download PDF

14. Haemoglobin thresholds to define anaemia from age 6 months to 65 years:estimates from international data sources

Author

Braat, Sabine, Fielding, Katherine L., Han, Jiru, Jackson, Victoria E., Zaloumis, Sophie, Xu, Jessica Xu Hui, Moir-Meyer, Gemma, Blaauwendraad, Sophia M., Jaddoe, Vincent W.V., Gaillard, Romy, Parkin, Patricia C., Borkhoff, Cornelia M., Keown-Stoneman, Charles D.G., Birken, Catherine S., Maguire, Jonathon L., Bahlo, Melanie, Davidson, Eliza M., Pasricha, Sant Rayn, Braat, Sabine, Fielding, Katherine L., Han, Jiru, Jackson, Victoria E., Zaloumis, Sophie, Xu, Jessica Xu Hui, Moir-Meyer, Gemma, Blaauwendraad, Sophia M., Jaddoe, Vincent W.V., Gaillard, Romy, Parkin, Patricia C., Borkhoff, Cornelia M., Keown-Stoneman, Charles D.G., Birken, Catherine S., Maguire, Jonathon L., Bahlo, Melanie, Davidson, Eliza M., and Pasricha, Sant Rayn

Abstract

Background: Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines. Methods: In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6–23 months, 24–59 months, 5–11 years, and 12–17 years, and adults aged 18–65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations. Findings: We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104·4 g/L (90% CI 103·5–105·3) in 924 children aged 6–23 months, 110·2 g/L (109·5–110·9) in 1874 children aged 24–59 months, and 114·4 g/L (113·6–115·2) in 1839 children aged 5–11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122·2 g/L (90% CI 121·3–123·1) in 1741 female adolescents aged 12–17 years and 128·2 g/L (126·4–130·0) in 1103 male adolescents aged 12–17 years. In pooled analyses of adults aged 18–65 years, the fifth centile was 119·7 g/L (90% CI 119·1–120·3) in 3640 non-pregnant females and 134·9 g/L (134·2–135·6) in 2377 males. Fifth centiles in pregnancy were 110

Published
2024

16. Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function

Author

Yang, Tianzhong, Jackson, Victoria E., Smith, Albert V., Chen, Han, Bartz, Traci M., Sitlani, Colleen M., Psaty, Bruce M., Gharib, Sina A., O’Connor, George T., Dupuis, Josée, Xu, Jiayi, Lohman, Kurt, Liu, Yongmei, Kritchevsky, Stephen B., Cassano, Patricia A., Flexeder, Claudia, Gieger, Christian, Karrasch, Stefan, Peters, Annette, Schulz, Holger, Harris, Sarah E., Starr, John M., Deary, Ian J., Manichaikul, Ani, Oelsner, Elizabeth C., Barr, R. G., Taylor, Kent D., Rich, Stephen S., Bonten, Tobias N., Mook-Kanamori, Dennis O., Noordam, Raymond, Li-Gao, Ruifang, Jarvelin, Marjo-Riitta, Wielscher, Matthias, Terzikhan, Natalie, Lahousse, Lies, Brusselle, Guy, Weiss, Stefan, Ewert, Ralf, Gläser, Sven, Homuth, Georg, Shrine, Nick, Hall, Ian P., Tobin, Martin, London, Stephanie J., Wei, Peng, and Morrison, Alanna C.

Published
2021
Full Text
View/download PDF

17. Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia

Author

Khan, Kamal, Zech, Michael, Morgan, Angela T., Amor, David J., Skorvanek, Matej, Khan, Tahir N., Hildebrand, Michael S., Jackson, Victoria E., Scerri, Thomas S., Coleman, Matthew, Rigbye, Kristin A., Scheffer, Ingrid E., Bahlo, Melanie, Wagner, Matias, Lam, Daniel D., Berutti, Riccardo, Havránková, Petra, Fečíková, Anna, Strom, Tim M., Han, Vladimir, Dosekova, Petra, Gdovinova, Zuzana, Laccone, Franco, Jameel, Muhammad, Mooney, Marie R., Baig, Shahid M., Jech, Robert, Davis, Erica E., Katsanis, Nicholas, and Winkelmann, Juliane

Published
2019
Full Text
View/download PDF

18. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author

Surendran, Praveen, Young, Robin, Barnes, Daniel R., Nielsen, Sune Fallgaard, Rasheed, Asif, Samuel, Maria, Zhao, Wei, Kontto, Jukka, Perola, Markus, Caslake, Muriel, de Craen, Anton J.M., Trompet, Stella, Uria-Nickelsen, Maria, Malarstig, Anders, Reily, Dermot F., Hoek, Maarten, Vogt, Thomas, Jukema, J. Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J., Alam, Dewan S., Majumder, Abdulla al Shafi, Di Angelantonio, Emanuele, Chowdhury, Rajiv, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrières, Jean, Kee, Frank, Kuulasmaa, Kari, Müller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, EPIC-CVD Consortium, Frossard, Philippe, Nordestgaard, Børge Grønne, Saleheen, Danish, Danesh, John, Butterworth, Adam S., Howson, Joanna M.M., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Melbourne, Carl A., Varga, Tibor V., Warren, Helen R., Tragante, Vinicius, Tachmazidou, Ioanna, Harris, Sarah E., Evangelou, Evangelos, Marten, Jonathan, Zhang, Weihua, Altmaier, Elisabeth, Luan, Jian’an, Langenberg, Claudia, Scott, Robert A., Yaghootkar, Hanieh, Stirrups, Kathleen, Kanoni, Stavroula, Marouli, Eirini, Karpe, Fredrik, Dominiczak, Anna F., Sever, Peter, Poulter, Neil, Rolandsson, Olov, Baumbach, Clemens, Afaq, Saima, Chambers, John C., Kooner, Jaspal S., Wareham, Nicholas J., Renström, Frida, Hallmans, Göran, Marioni, Riccardo E., Corley, Janie, Starr, John M., Verweij, Niek, de Boer, Rudolf A., van der Meer, Peter, Yavas, Ersin, Vaartjes, Ilonca, Bots, Michiel L., Asselbergs, Folkert W., Grabe, Hans J., Völzke, Henry, Nauck, Matthias, Weiss, Stefan, Pharoah, Paul D.P., Dunning, Alison M., Dennis, Joe G., Thompson, Deborah J., Michailidou, Kyriaki, Easton, Douglas F., Antoniou, Antonis C., Tyrrell, Jessica, Mihailov, Evelin, Samani, Nilesh J., Zhou, Kaixin, Neville, Matthew J., Metspalu, Andres, Palmer, Colin N.A., Hall, Ian P., Strachan, David P., Deary, Ian J., Frayling, Tim M., Hayward, Caroline, van der Harst, Pim, Zeggini, Eleftheria, Understanding Society Scientific Group, Munroe, Patricia B., Jansson, Jan-Håkan, Franks, Paul W., Deloukas, Panos, Caulfield, Mark J., Wain, Louise V., Tobin, Martin D., Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valérie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Bertelsen, Sarah, Chou, Yi-Ling, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Kardia, Sharon L.R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, McGue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Weir, David R., Kaprio, Jaakko, Abecasis, Gonçalo R., Liu, Dajiang J., and Vrieze, Scott

Published
2019
Full Text
View/download PDF

19. New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Shrine, Nick, Guyatt, Anna L., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Hobbs, Brian D., Melbourne, Carl A., Batini, Chiara, Fawcett, Katherine A., Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F., Obeidat, Ma’en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Sun, Benjamin B., Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E, Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J., Bakke, Per S., Beaty, Terri H., Bleecker, Eugene R., Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D., Danesh, John, DeMeo, Dawn L., Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L., Hao, Ke, Hoffman, Joshua D., Hokanson, John E., Homuth, Georg, Joshi, Peter K., Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian’an, Mahajan, Anubha, Maranville, Joseph C., Murray, Alison, Nickle, David C., Packer, Richard, Parker, Margaret M., Paynton, Megan L., Porteous, David J., Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Sin, Don D, Smith, Blair H, Soler Artigas, María, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul R. H. J., Van den Berge, Maarten, Whittaker, John C., Woodruff, Prescott G., Yerges-Armstrong, Laura M., Troyanskaya, Olga G., Raitakari, Olli T., Kähönen, Mika, Polašek, 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, Silverman, Edwin K., Hayward, Caroline, Morris, Andrew P., Butterworth, Adam S., Scott, Robert A., Walters, Robin G., Meyers, Deborah A., Cho, Michael H., Strachan, David P., Hall, Ian P., Tobin, Martin D., and Wain, Louise V.

Published
2019
Full Text
View/download PDF

20. 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., and Cho, Michael H.

Published
2019
Full Text
View/download PDF

21. Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40

Author

Morgan, Angela T, primary, Scerri, Thomas S, additional, Vogel, Adam P, additional, Reid, Christopher A, additional, Quach, Mara, additional, Jackson, Victoria E, additional, McKenzie, Chaseley, additional, Burrows, Emma L, additional, Bennett, Mark F, additional, Turner, Samantha J, additional, Reilly, Sheena, additional, Horton, Sarah E, additional, Block, Susan, additional, Kefalianos, Elaina, additional, Frigerio-Domingues, Carlos, additional, Sainz, Eduardo, additional, Rigbye, Kristin A, additional, Featherby, Travis J, additional, Richards, Kay L, additional, Kueh, Andrew, additional, Herold, Marco J, additional, Corbett, Mark A, additional, Gecz, Jozef, additional, Helbig, Ingo, additional, Thompson-Lake, Daisy G Y, additional, Liégeois, Frédérique J, additional, Morell, Robert J, additional, Hung, Andrew, additional, Drayna, Dennis, additional, Scheffer, Ingrid E, additional, Wright, David K, additional, Bahlo, Melanie, additional, and Hildebrand, Michael S, additional

Published
2023
Full Text
View/download PDF

23. A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction

Author

Hildebrand, Joanne M., Kauppi, Maria, Majewski, Ian J., Liu, Zikou, Cox, Allison J., Miyake, Sanae, Petrie, Emma J., Silk, Michael A., Li, Zhixiu, Tanzer, Maria C., Brumatti, Gabriela, Young, Samuel N., Hall, Cathrine, Garnish, Sarah E., Corbin, Jason, Stutz, Michael D., Di Rago, Ladina, Gangatirkar, Pradnya, Josefsson, Emma C., Rigbye, Kristin, Anderton, Holly, Rickard, James A., Tripaydonis, Anne, Sheridan, Julie, Scerri, Thomas S., Jackson, Victoria E., Czabotar, Peter E., Zhang, Jian-Guo, Varghese, Leila, Allison, Cody C., Pellegrini, Marc, Tannahill, Gillian M., Hatchell, Esme C., Willson, Tracy A., Stockwell, Dina, de Graaf, Carolyn A., Collinge, Janelle, Hilton, Adrienne, Silke, Natasha, Spall, Sukhdeep K., Chau, Diep, Athanasopoulos, Vicki, Metcalf, Donald, Laxer, Ronald M., Bassuk, Alexander G., Darbro, Benjamin W., Fiatarone Singh, Maria A., Vlahovich, Nicole, Hughes, David, Kozlovskaia, Maria, Ascher, David B., Warnatz, Klaus, Venhoff, Nils, Thiel, Jens, Biben, Christine, Blum, Stefan, Reveille, John, Hildebrand, Michael S., Vinuesa, Carola G., McCombe, Pamela, Brown, Matthew A., Kile, Benjamin T., McLean, Catriona, Bahlo, Melanie, Masters, Seth L., Nakano, Hiroyasu, Ferguson, Polly J., Murphy, James M., Alexander, Warren S., and Silke, John

Published
2020
Full Text
View/download PDF

24. Severe childhood speech disorder: Gene discovery highlights transcriptional dysregulation

Author

Hildebrand, Michael S., Jackson, Victoria E., Scerri, Thomas S., Van Reyk, Olivia, Coleman, Matthew, Braden, Ruth O., Turner, Samantha, Rigbye, Kristin A., Boys, Amber, Barton, Sarah, Webster, Richard, Fahey, Michael, Saunders, Kerryn, Parry-Fielder, Bronwyn, Paxton, Georgia, Hayman, Michael, Coman, David, Goel, Himanshu, Baxter, Anne, Ma, Alan, Davis, Noni, Reilly, Sheena, Delatycki, Martin, Liégeois, Frederique J., Connelly, Alan, Gecz, Jozef, Fisher, Simon E., Amor, David J., Scheffer, Ingrid E., Bahlo, Melanie, and Morgan, Angela T.

Published
2020
Full Text
View/download PDF

25. Multi-omic spatial effects on high-resolution AI-derived retinal thickness

Author

Jackson, Victoria E, primary, Wu, Yue, additional, Bonelli, Roberto, additional, Owen, Julia, additional, Farashi, Samaneh, additional, Kihara, Yuka, additional, Gantner, Marin L, additional, Egan, Catherine, additional, Williams, Katie M, additional, Ansell, Brendan RE, additional, Tufail, Adnan, additional, Lee, Aaron Y, additional, and Bahlo, Melanie, additional

Published
2023
Full Text
View/download PDF

26. Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank

Author

Wain, Louise V, Shrine, Nick, Miller, Suzanne, Jackson, Victoria E, Ntalla, Ioanna, Artigas, María Soler, Billington, Charlotte K, Kheirallah, Abdul Kader, Allen, Richard, Cook, James P, Probert, Kelly, Obeidat, Ma'en, Bossé, Yohan, Hao, Ke, Postma, Dirkje S, Paré, Peter D, Ramasamy, Adaikalavan, Mägi, Reedik, Mihailov, Evelin, Reinmaa, Eva, Melén, Erik, O'Connell, Jared, Frangou, Eleni, Delaneau, Olivier, Freeman, Colin, Petkova, Desislava, McCarthy, Mark, Sayers, Ian, Deloukas, Panos, Hubbard, Richard, Pavord, Ian, Hansell, Anna L, Thomson, Neil C, Zeggini, Eleftheria, Morris, Andrew P, Marchini, Jonathan, Strachan, David P, Tobin, Martin D, and Hall, Ian P

Published
2015
Full Text
View/download PDF

27. Statistical haemoglobin thresholds to define anaemia across the lifecycle

Author

Braat, Sabine, Fielding, Katherine, Han, Jiru, Jackson, Victoria E., Zaloumis, Sophie, Xu, Jessica Xu Hui, Moir-Meyer, Gemma, Blaauwendraad, Sophia M., Jaddoe, Vincent W.V., Gaillard, Romy, Parkin, Patricia C., Borkhoff, Cornelia M., Keown-Stoneman, Charles D.G., Birken, Catherine S., Maguire, Jonathon L., Bahlo, Melanie, Davidson, Eliza, and Pasricha, Sant-Rayn

Subjects
Article
Abstract

Detection of anaemia is critical for clinical medicine and public health. Current WHO values that define anaemia are statistical thresholds (5 (th) centile) set over 50 years ago, and are presently

Published
2023

28. Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia

Author

Ware, James S., Wain, Louise V., Channavajjhala, Sarath K., Jackson, Victoria E., Edwards, Elizabeth, Lu, Run, Siew, Keith, Jia, Wenjing, Shrine, Nick, Kinnear, Sue, Jalland, Mahli, Henry, Amanda P., Clayton, Jenny, O'Shaughnessy, Kevin M., Tobin, Martin D., Schuster, Victor L., Cook, Stuart, Hall, Ian P., and Glover, Mark

Subjects
Observations, Genetic aspects, Phenotypes -- Observations, Hyponatremia -- Genetic aspects, Pharmacogenomics -- Observations
Abstract

Introduction Cardiovascular disease is the leading cause of mortality worldwide (1, 2) and hypertension one of its most important modifiable causes. Thiazide diuretics inhibit the thiazide-sensitive sodium chloride cotransporter NCC [...], Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin [E.sub.2] excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions associated with TIH. We identified a suggestive association with a variant in SLCO2A1, which encodes a prostaglandin transporter in the distal nephron. Resequencing of SLCO2A1 revealed a nonsynonymous variant, rs34550074 (p.A396T), and association with this SNP was replicated in a second cohort of TIH cases. TIH patients with the p.A396T variant demonstrated increased urinary excretion of prostaglandin [E.sub.2] and metabolites. Moreover, the SLCO2A1 phospho-mimic p.A396E showed loss of transporter function in vitro. These findings indicate that the phenotype of TIH involves a more extensive metabolic derangement than previously recognized. We propose one mechanism underlying TIH development in a subgroup of patients in which SLCO2A1 regulation is altered.

Published
2017
Full Text
View/download PDF

29. Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

Author

Kaspi, Antony, primary, Hildebrand, Michael S., additional, Jackson, Victoria E., additional, Braden, Ruth, additional, van Reyk, Olivia, additional, Howell, Tegan, additional, Debono, Simone, additional, Lauretta, Mariana, additional, Morison, Lottie, additional, Coleman, Matthew J., additional, Webster, Richard, additional, Coman, David, additional, Goel, Himanshu, additional, Wallis, Mathew, additional, Dabscheck, Gabriel, additional, Downie, Lilian, additional, Baker, Emma K., additional, Parry-Fielder, Bronwyn, additional, Ballard, Kirrie, additional, Harrold, Eva, additional, Ziegenfusz, Shaun, additional, Bennett, Mark F., additional, Robertson, Erandee, additional, Wang, Longfei, additional, Boys, Amber, additional, Fisher, Simon E., additional, Amor, David J., additional, Scheffer, Ingrid E., additional, Bahlo, Melanie, additional, and Morgan, Angela T., additional

Published
2022
Full Text
View/download PDF

30. Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Shrine, Nick, Guyatt, Anna L., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Hobbs, Brian D., Melbourne, Carl A., Batini, Chiara, Fawcett, Katherine A., Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F., Obeidat, Ma’en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Sun, Benjamin B., Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E, Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J., Bakke, Per S., Beaty, Terri H., Bleecker, Eugene R., Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D., Danesh, John, DeMeo, Dawn L., Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L., Hao, Ke, Hoffman, Joshua D., Hokanson, John E., Homuth, Georg, Joshi, Peter K., Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian’an, Mahajan, Anubha, Maranville, Joseph C., Murray, Alison, Nickle, David C., Packer, Richard, Parker, Margaret M., Paynton, Megan L., Porteous, David J., Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Sin, Don D, Smith, Blair H, Artigas, María Soler, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul R. H. J., Van den Berge, Maarten, Whittaker, John C., Woodruff, Prescott G., Yerges-Armstrong, Laura M., Troyanskaya, Olga G., Raitakari, Olli T., Kähönen, Mika, Polašek, 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, Silverman, Edwin K., Hayward, Caroline, Morris, Andrew P., Butterworth, Adam S., Scott, Robert A., Walters, Robin G., Meyers, Deborah A., Cho, Michael H., Strachan, David P., Hall, Ian P., Tobin, Martin D., and Wain, Louise V.

Published
2019
Full Text
View/download PDF

32. Iron homeostasis governs erythroid phenotype in Polycythemia Vera

Author

Bennett, Cavan, primary, Jackson, Victoria E, additional, Pettikiriarachchi, Anne, additional, Hayman, Thomas, additional, Schaeper, Ute, additional, Moir-Meyer, Gemma, additional, Fielding, Katherine, additional, Ataide, Ricardo, additional, Clucas, Danielle, additional, Baldi, Andrew, additional, Garnham, Alexandra L, additional, Li-Wai-Suen, Connie SN, additional, Alexander, Warren S, additional, Bahlo, Melanie, additional, Burbury, Kate, additional, Ng, Ashley P, additional, and Pasricha, Sant-Rayn, additional

Published
2022
Full Text
View/download PDF

33. Self‐reported impact of developmental stuttering across the lifespan

Author

Boyce, Jessica O., primary, Jackson, Victoria E., additional, van Reyk, Olivia, additional, Parker, Richard, additional, Vogel, Adam P., additional, Eising, Else, additional, Horton, Sarah E., additional, Gillespie, Nathan A., additional, Scheffer, Ingrid E., additional, Amor, David J., additional, Hildebrand, Michael S., additional, Fisher, Simon E., additional, Martin, Nicholas G., additional, Reilly, Sheena, additional, Bahlo, Melanie, additional, and Morgan, Angela T., additional

Published
2022
Full Text
View/download PDF

34. Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12

Author

Jackson, Victoria E, Ntalla, Ioanna, Sayers, Ian, Morris, Richard, Whincup, Peter, Casas, Juan-Pablo, Amuzu, Antoinette, Choi, Minkyoung, Dale, Caroline, Kumari, Meena, Engmann, Jorgen, Kalsheker, Noor, Chappell, Sally, Guetta-Baranes, Tamar, McKeever, Tricia M, Palmer, Colin N A, Tavendale, Roger, Holloway, John W, Sayer, Avan A, Dennison, Elaine M, Cooper, Cyrus, Bafadhel, Mona, Barker, Bethan, Brightling, Chris, Bolton, Charlotte E, John, Michelle E, Parker, Stuart G, Moffat, Miriam F, Wardlaw, Andrew J, Connolly, Martin J, Porteous, David J, Smith, Blair H, Padmanabhan, Sandosh, Hocking, Lynne, Stirrups, Kathleen E, Deloukas, Panos, Strachan, David P, Hall, Ian P, Tobin, Martin D, and Wain, Louise V

Published
2016
Full Text
View/download PDF

36. A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease

Author

Moll, Matthew, primary, Jackson, Victoria E., additional, Yu, Bing, additional, Grove, Megan L., additional, London, Stephanie J., additional, Gharib, Sina A., additional, Bartz, Traci M., additional, Sitlani, Colleen M., additional, Dupuis, Josée, additional, O’Connor, George T., additional, Xu, Hanfei, additional, Cassano, Patricia A., additional, Patchen, Bonnie Kaufmann, additional, Kim, Woo Jin, additional, Park, Jinkyeong, additional, Kim, Kun Hee, additional, Han, Buhm, additional, Barr, R. Graham, additional, Manichaikul, Ani, additional, Nguyen, Jennifer N., additional, Rich, Stephen S., additional, Lahousse, Lies, additional, Terzikhan, Natalie, additional, Brusselle, Guy, additional, Sakornsakolpat, Phuwanat, additional, Liu, Jiangyuan, additional, Benway, Christopher J., additional, Hall, Ian P., additional, Tobin, Martin D., additional, Wain, Louise V., additional, Silverman, Edwin K., additional, Cho, Michael H., additional, and Hobbs, Brian D., additional

Published
2021
Full Text
View/download PDF

37. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A Mesut, Liu, Mengzhen, Jackson, Victoria E, Barnes, Daniel R, Datta, Gargi, Melbourne, Carl A, Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C, Asselbergs, Folkert W, Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Karpe, Fredrik, Nielsen, Sune Fallgaard, Varga, Tibor V, Chen, Fang, Nordestgaard, Børge Grønne, Cardiovascular Centre (CVC), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Subjects
RISK, LUNG-CANCER, DATABASE, LD SCORE REGRESSION, BIOLOGICAL INSIGHTS, MENDELIAN RANDOMIZATION, EFFICIENT, CIGARETTE-SMOKING, GENOME-WIDE ASSOCIATION, DISEASE
Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P

Published
2020
Full Text
View/download PDF

38. A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease

Author

Moll, Matthew, Jackson, Victoria E., Yu, Bing, Grove, Megan L., London, Stephanie J., Gharib, Sina A., Bartz, Traci M., Sitlani, Colleen M., Dupuis, Josee, O’Connor, George T., Xu, Hanfei, Cassano, Patricia A., Patchen, Bonnie Kaufmann, Kim, Woo Jin, Park, Jinkyeong, Kim, Kun Hee, Han, Buhm, Barr, R. Graham, Manichaikul, Ani, Nguyen, Jennifer N., Rich, Stephen S., Lahousse, Lies, Terzikhan, Natalie, Brusselle, Guy, Sakornsakolpat, Phuwanat, Liu, Jiangyuan, Benway, Christopher J., Hall, Ian P., Tobin, Martin D., Wain, Louise V., Silverman, Edwin K., Cho, Michael H., Hobbs, Brian D., Moll, Matthew, Jackson, Victoria E., Yu, Bing, Grove, Megan L., London, Stephanie J., Gharib, Sina A., Bartz, Traci M., Sitlani, Colleen M., Dupuis, Josee, O’Connor, George T., Xu, Hanfei, Cassano, Patricia A., Patchen, Bonnie Kaufmann, Kim, Woo Jin, Park, Jinkyeong, Kim, Kun Hee, Han, Buhm, Barr, R. Graham, Manichaikul, Ani, Nguyen, Jennifer N., Rich, Stephen S., Lahousse, Lies, Terzikhan, Natalie, Brusselle, Guy, Sakornsakolpat, Phuwanat, Liu, Jiangyuan, Benway, Christopher J., Hall, Ian P., Tobin, Martin D., Wain, Louise V., Silverman, Edwin K., Cho, Michael H., and Hobbs, Brian D.

Abstract

Genome-wide association studies (GWASs) have identified regions associated with chronic obstructive pulmonary disease (COPD). GWASs of other diseases have shown an approximately 10-fold overrepresentation of nonsynonymous variants, despite limited exonic coverage on genotyping arrays. We hypothesized that a large-scale analysis of coding variants could discover novel genetic associations with COPD, including rare variants with large effect sizes. We performed a meta-analysis of exome arrays from 218,399 controls and 33,851 moderate-to-severe COPD cases. All exome-wide significant associations were present in regions previously identified by GWAS. We did not identify any novel rare coding variants with large effect sizes. Within GWAS regions on chromosomes 5q, 6p, and 15q, four coding variants were conditionally significant (P < 0.00015) when adjusting for lead GWAS single-nucleotide polymorphisms A common gasdermin B (GSDMB) splice variant (rs11078928) previously associated with a decreased risk for asthma was nominally associated with a decreased risk for COPD [minor allele frequency (MAF)=0.46, P = 1.8e-4]. Two stop variants in coiled-coil a-helical rod protein 1 (CCHCR1), a gene involved in regulating cell proliferation, were associated with COPD (both P < 0.0001). The SERPINA1 Z allele was associated with a random-effects odds ratio of 1.43 for COPD (95% confidence interval = 1.17–1.74), though with marked heterogeneity across studies. Overall, COPD-associated exonic variants were identified in genes involved in DNA methylation, cell-matrix interactions, cell proliferation, and cell death. In conclusion, we performed the largest exome array meta-analysis of COPD to date and identified potential functional coding variants. Future studies are needed to identify rarer variants and further define the role of coding variants in COPD pathogenesis.

Published
2021

39. Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Author

Moll, Matthew, primary, Sakornsakolpat, Phuwanat, additional, Shrine, Nick, additional, Hobbs, Brian D, additional, DeMeo, Dawn L, additional, John, Catherine, additional, Guyatt, Anna L, additional, McGeachie, Michael J, additional, Gharib, Sina A, additional, Obeidat, Ma'en, additional, Lahousse, Lies, additional, Wijnant, Sara R A, additional, Brusselle, Guy, additional, Meyers, Deborah A, additional, Bleecker, Eugene R, additional, Li, Xingnan, additional, Tal-Singer, Ruth, additional, Manichaikul, Ani, additional, Rich, Stephen S, additional, Won, Sungho, additional, Kim, Woo Jin, additional, Do, Ah Ra, additional, Washko, George R, additional, Barr, R Graham, additional, Psaty, Bruce M, additional, Bartz, Traci M, additional, Hansel, Nadia N, additional, Barnes, Kathleen, additional, Hokanson, John E, additional, Crapo, James D, additional, Lynch, David, additional, Bakke, Per, additional, Gulsvik, Amund, additional, Hall, Ian P, additional, Wain, Louise, additional, Weiss, Scott T, additional, Silverman, Edwin K, additional, Dudbridge, Frank, additional, Tobin, Martin D, additional, Cho, Michael H, additional, Soler Artigas, María, additional, Jackson, Victoria E, additional, Strachan, David P, additional, Hui, Jennie, additional, James, Alan L, additional, Kerr, Shona M, additional, Polasek, Ozren, additional, Vitart, Veronique, additional, Marten, Jonathan, additional, Rudan, Igor, additional, Kähönen, Mika, additional, Surakka, Ida, additional, Gieger, Christian, additional, Karrasch, Stefan, additional, Rawal, Rajesh, additional, Schulz, Holger, additional, Deary, Ian J, additional, Harris, Sarah E, additional, Enroth, Stefan, additional, Gyllensten, Ulf, additional, Imboden, Medea, additional, Probst-Hensch, Nicole M, additional, Lehtimäki, Terho, additional, Raitakari, Olli T, additional, Langenberg, Claudia, additional, Luan, Jian'an, additional, Wareham, Nick, additional, Zhao, Jing Hua, additional, Hayward, Caroline, additional, Murray, Alison, additional, Porteous, David J, additional, Smith, Blair H, additional, Jarvelin, Marjo-Riitta, additional, Wielscher, Matthias, additional, Joshi, Peter K, additional, Kentistou, Katherine A, additional, Timmers, Paul RHJ, additional, Wilson, James F, additional, Cook, James P, additional, Lind, Lars, additional, Mahajan, Anubha, additional, Morris, Andrew P, additional, Ewert, Ralf, additional, Homuth, Georg, additional, Stubbe, Beate, additional, Weiss, Stefan, additional, and Zeggini, Eleftheria, additional

Published
2020
Full Text
View/download PDF

40. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L., Brazel, David M., Chambers, John C., Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi Ling, David, Sean P., de Boer, Rudolf A., de Leeuw, Christiaan A., Dennis, Joe G., Dominiczak, Anna F., Dunning, Alison M., Easton, Douglas F., Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D., Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J., Polderman, Tinca J., Posthuma, Danielle, van der Meer, Peter, Verweij, Niek, Jiang, Yu, Zhao, Wei, Chowdhury, Rajiv, Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L., Brazel, David M., Chambers, John C., Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi Ling, David, Sean P., de Boer, Rudolf A., de Leeuw, Christiaan A., Dennis, Joe G., Dominiczak, Anna F., Dunning, Alison M., Easton, Douglas F., Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D., Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J., Polderman, Tinca J., Posthuma, Danielle, van der Meer, Peter, Verweij, Niek, Jiang, Yu, Zhao, Wei, and Chowdhury, Rajiv

Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10−8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10−8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10−3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Published
2020

41. A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction.

Author

UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/SIGN - Cell signalling, Hildebrand, Joanne M, Kauppi, Maria, Majewski, Ian J, Liu, Zikou, Cox, Allison J, Miyake, Sanae, Petrie, Emma J, Silk, Michael A, Li, Zhixiu, Tanzer, Maria C, Brumatti, Gabriela, Young, Samuel N, Hall, Cathrine, Garnish, Sarah E, Corbin, Jason, Stutz, Michael D, Di Rago, Ladina, Gangatirkar, Pradnya, Josefsson, Emma C, Rigbye, Kristin, Anderton, Holly, Rickard, James A, Tripaydonis, Anne, Sheridan, Julie, Scerri, Thomas S, Jackson, Victoria E, Czabotar, Peter E, Zhang, Jian-Guo, Varghese, Leila, Allison, Cody C, Pellegrini, Marc, Tannahill, Gillian M, Hatchell, Esme C, Willson, Tracy A, Stockwell, Dina, de Graaf, Carolyn A, Collinge, Janelle, Hilton, Adrienne, Silke, Natasha, Spall, Sukhdeep K, Chau, Diep, Athanasopoulos, Vicki, Metcalf, Donald, Laxer, Ronald M, Bassuk, Alexander G, Darbro, Benjamin W, Fiatarone Singh, Maria A, Vlahovich, Nicole, Hughes, David, Kozlovskaia, Maria, Ascher, David B, Warnatz, Klaus, Venhoff, Nils, Thiel, Jens, Biben, Christine, Blum, Stefan, Reveille, John, Hildebrand, Michael S, Vinuesa, Carola G, McCombe, Pamela, Brown, Matthew A, Kile, Benjamin T, McLean, Catriona, Bahlo, Melanie, Masters, Seth L, Nakano, Hiroyasu, Ferguson, Polly J, Murphy, James M, Alexander, Warren S, Silke, John, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/SIGN - Cell signalling, Hildebrand, Joanne M, Kauppi, Maria, Majewski, Ian J, Liu, Zikou, Cox, Allison J, Miyake, Sanae, Petrie, Emma J, Silk, Michael A, Li, Zhixiu, Tanzer, Maria C, Brumatti, Gabriela, Young, Samuel N, Hall, Cathrine, Garnish, Sarah E, Corbin, Jason, Stutz, Michael D, Di Rago, Ladina, Gangatirkar, Pradnya, Josefsson, Emma C, Rigbye, Kristin, Anderton, Holly, Rickard, James A, Tripaydonis, Anne, Sheridan, Julie, Scerri, Thomas S, Jackson, Victoria E, Czabotar, Peter E, Zhang, Jian-Guo, Varghese, Leila, Allison, Cody C, Pellegrini, Marc, Tannahill, Gillian M, Hatchell, Esme C, Willson, Tracy A, Stockwell, Dina, de Graaf, Carolyn A, Collinge, Janelle, Hilton, Adrienne, Silke, Natasha, Spall, Sukhdeep K, Chau, Diep, Athanasopoulos, Vicki, Metcalf, Donald, Laxer, Ronald M, Bassuk, Alexander G, Darbro, Benjamin W, Fiatarone Singh, Maria A, Vlahovich, Nicole, Hughes, David, Kozlovskaia, Maria, Ascher, David B, Warnatz, Klaus, Venhoff, Nils, Thiel, Jens, Biben, Christine, Blum, Stefan, Reveille, John, Hildebrand, Michael S, Vinuesa, Carola G, McCombe, Pamela, Brown, Matthew A, Kile, Benjamin T, McLean, Catriona, Bahlo, Melanie, Masters, Seth L, Nakano, Hiroyasu, Ferguson, Polly J, Murphy, James M, Alexander, Warren S, and Silke, John

Abstract

MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, Mlkl, that alters the two-helix 'brace' that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of Mlkl homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO).

Published
2020

42. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author

Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valerie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Barnes, Daniel R., Bertelsen, Sarah, Chou, Yi-Ling, Erzurumluoglu, A. Mesut, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Melbourne, Carl A., Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Zhao, Wei, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Howson, Joanna M. M., Kardia, Sharon L. R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, Mcgue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Tobin, Martin D., Weir, David R., Kaprio, Jaakko, Abecasis, Goncalo R., Liu, Dajiang J., Vrieze, Scott, Surendran, Praveen, Young, Robin, Nielsen, Sune Fallgaard, Rasheed, Asif, Samuel, Maria, Kontto, Jukka, Perola, Markus, Caslake, Muriel, de Craen, Anton J. M., Trompet, Stella, Uria-Nickelsen, Maria, Malarstig, Anders, Reily, Dermot F., Hoek, Maarten, Vogt, Thomas, Jukema, J. Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J., Alam, Dewan S., Majumder, Abdulla al Shafi, Di Ange-Lantonio, Emanuele, Chowdhury, Rajiv, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrieres, Jean, Kee, Frank, Kuulasmaa, Kari, Mueller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, Frossard, Philippe, Nordestgaard, Borge Gronne, Saleheen, Danish, Danesh, John, Butterworth, Adam S., Jackson, Victoria E., Varga, Tibor V., Warren, Helen R., Tragante, Vinicius, Tachmazidou, Ioanna, Harris, Sarah E., Evangelou, Evangelos, Marten, Jonathan, Zhang, Weihua, Altmaier, Elisabeth, Luan, Jian'an, Langenberg, Claudia, Scott, Robert A., Yaghootkar, Hanieh, Stirrups, Kathleen, Kanoni, Stavroula, Marouli, Eirini, Karpe, Fredrik, Dominiczak, Anna F., Sever, Peter, Poulter, Neil, Rolandsson, Olov, Baumbach, Clemens, Afaq, Saima, Chambers, John C., Kooner, Jaspal S., Wareham, Nicholas J., Renstrom, Frida, Hallmans, Goran, Marioni, Riccardo E., Corley, Janie, Starr, John M., Verweij, Niek, de Boer, Rudolf A., van der Meer, Peter, Yavas, Ersin, Vaartjes, Ilonca, Bots, Michiel L., Asselbergs, Folkert W., Grabe, Hans J., Volzke, Henry, Nauck, Matthias, Weiss, Stefan, Pharoah, Paul D. P., Dunning, Alison M., Dennis, Joe G., Thompson, Deborah J., Michailidou, Kyriaki, Easton, Douglas F., Antoniou, Antonis C., Tyrrell, Jessica, Mihailov, Evelin, Samani, Nilesh J., Zhou, Kaixin, Neville, Matthew J., Metspalu, Andres, Palmer, Colin N. A., Hall, Ian P., Strachan, David P., Deary, Ian J., Frayling, Tim M., Hayward, Caroline, van der Harst, Pim, Zeggini, Eleftheria, Munroe, Patricia B., Jansson, Jan-Hakan, Franks, Paul W., Deloukas, Panos, Caulfield, Mark J., Wain, Louise V., Brazel, David M., Jiang, Yu, Hughey, Jordan M., Turcot, Valerie, Zhan, Xiaowei, Gong, Jian, Batini, Chiara, Weissenkampen, J. Dylan, Liu, MengZhen, Barnes, Daniel R., Bertelsen, Sarah, Chou, Yi-Ling, Erzurumluoglu, A. Mesut, Faul, Jessica D., Haessler, Jeff, Hammerschlag, Anke R., Hsu, Chris, Kapoor, Manav, Lai, Dongbing, Le, Nhung, de Leeuw, Christiaan A., Loukola, Anu, Mangino, Massimo, Melbourne, Carl A., Pistis, Giorgio, Qaiser, Beenish, Rohde, Rebecca, Shao, Yaming, Stringham, Heather, Wetherill, Leah, Zhao, Wei, Agrawal, Arpana, Bierut, Laura, Chen, Chu, Eaton, Charles B., Goate, Alison, Haiman, Christopher, Heath, Andrew, Iacono, William G., Martin, Nicholas G., Polderman, Tinca J., Reiner, Alex, Rice, John, Schlessinger, David, Scholte, H. Steven, Smith, Jennifer A., Tardif, Jean-Claude, Tindle, Hilary A., van der Leij, Andries R., Boehnke, Michael, Chang-Claude, Jenny, Cucca, Francesco, David, Sean P., Foroud, Tatiana, Howson, Joanna M. M., Kardia, Sharon L. R., Kooperberg, Charles, Laakso, Markku, Lettre, Guillaume, Madden, Pamela, Mcgue, Matt, North, Kari, Posthuma, Danielle, Spector, Timothy, Stram, Daniel, Tobin, Martin D., Weir, David R., Kaprio, Jaakko, Abecasis, Goncalo R., Liu, Dajiang J., Vrieze, Scott, Surendran, Praveen, Young, Robin, Nielsen, Sune Fallgaard, Rasheed, Asif, Samuel, Maria, Kontto, Jukka, Perola, Markus, Caslake, Muriel, de Craen, Anton J. M., Trompet, Stella, Uria-Nickelsen, Maria, Malarstig, Anders, Reily, Dermot F., Hoek, Maarten, Vogt, Thomas, Jukema, J. Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J., Alam, Dewan S., Majumder, Abdulla al Shafi, Di Ange-Lantonio, Emanuele, Chowdhury, Rajiv, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrieres, Jean, Kee, Frank, Kuulasmaa, Kari, Mueller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, Frossard, Philippe, Nordestgaard, Borge Gronne, Saleheen, Danish, Danesh, John, Butterworth, Adam S., Jackson, Victoria E., Varga, Tibor V., Warren, Helen R., Tragante, Vinicius, Tachmazidou, Ioanna, Harris, Sarah E., Evangelou, Evangelos, Marten, Jonathan, Zhang, Weihua, Altmaier, Elisabeth, Luan, Jian'an, Langenberg, Claudia, Scott, Robert A., Yaghootkar, Hanieh, Stirrups, Kathleen, Kanoni, Stavroula, Marouli, Eirini, Karpe, Fredrik, Dominiczak, Anna F., Sever, Peter, Poulter, Neil, Rolandsson, Olov, Baumbach, Clemens, Afaq, Saima, Chambers, John C., Kooner, Jaspal S., Wareham, Nicholas J., Renstrom, Frida, Hallmans, Goran, Marioni, Riccardo E., Corley, Janie, Starr, John M., Verweij, Niek, de Boer, Rudolf A., van der Meer, Peter, Yavas, Ersin, Vaartjes, Ilonca, Bots, Michiel L., Asselbergs, Folkert W., Grabe, Hans J., Volzke, Henry, Nauck, Matthias, Weiss, Stefan, Pharoah, Paul D. P., Dunning, Alison M., Dennis, Joe G., Thompson, Deborah J., Michailidou, Kyriaki, Easton, Douglas F., Antoniou, Antonis C., Tyrrell, Jessica, Mihailov, Evelin, Samani, Nilesh J., Zhou, Kaixin, Neville, Matthew J., Metspalu, Andres, Palmer, Colin N. A., Hall, Ian P., Strachan, David P., Deary, Ian J., Frayling, Tim M., Hayward, Caroline, van der Harst, Pim, Zeggini, Eleftheria, Munroe, Patricia B., Jansson, Jan-Hakan, Franks, Paul W., Deloukas, Panos, Caulfield, Mark J., and Wain, Louise V.

Published
2019

43. Meta-analysis of exome array data identifies six novel genetic loci for lung function [version 1; peer review: 1 approved, 1 approved with reservations]

Author

Jackson, Victoria E., Latourelle, Jeanne C., Wain, Louise V., Smith, Albert V., Grove, Megan L., Bartz, Traci M., Obeidat, Ma’En, Province, Michael A., Gao, Wei, Qaiser, Beenish, Porteous, David J., Cassano, Patricia A., Ahluwalia, Tarunveer S., Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E., Manichaikul, Ani, Pottinger, Tess D., Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M., Brody, Jennifer A., Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M., Linneberg, Allan, Lange, Leslie A., Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E., Brusselle, Guy G., Hansen, Torben, Uitterlinden, André G., Ikram, M. Arfan, Dupuis, Josée, Epidemiology, Erasmus School of Economics, Department of Finance, Internal Medicine, and Radiology & Nuclear Medicine

Abstract

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P

Published
2018

44. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Author

Wain, Louise V., Shrine, Nick, Erzurumluoglu, A. Mesut, Noyvert, Boris, Bossini-Castillo, Lara, Henry, Amanda P., Portelli, Michael A., Hall, Robert J., Billington, Charlotte K., Rimington, Tracy L., Fenech, Anthony G., Johnson, Catherine, Blake, Tineka, Jackson, Victoria E., Allen, Richard J., Prins, Bram P., Campbell, Archie, Sayers, Ian, and Hall, Ian P.

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

Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20–1.27), P = 5.05 × 10−49), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

Published
2017

45. New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Shrine, Nick, primary, Guyatt, Anna L, additional, Erzurumluoglu, A Mesut, additional, Jackson, Victoria E, additional, Hobbs, Brian D, additional, Melbourne, Carl, additional, Batini, Chiara, additional, Fawcett, Katherine A, additional, Song, Kijoung, additional, Sakornsakolpat, Phuwanat, additional, Li, Xingnan, additional, Boxall, Ruth, additional, Reeve, Nicola F, additional, Obeidat, Ma’en, additional, Zhao, Jing Hua, additional, Wielscher, Matthias, additional, Society Scientific Group, Understanding, additional, Weiss, Stefan, additional, Kentistou, Katherine A, additional, Cook, James P, additional, Sun, Benjamin B, additional, Zhou, Jian, additional, Hui, Jennie, additional, Karrasch, Stefan, additional, Imboden, Medea, additional, Harris, Sarah E, additional, Marten, Jonathan, additional, Enroth, Stefan, additional, Kerr, Shona M, additional, Surakka, Ida, additional, Vitart, Veronique, additional, Lehtimäki, Terho, additional, Allen, Richard J, additional, Bakke, Per S, additional, Beaty, Terri H, additional, Bleecker, Eugene R, additional, Bossé, Yohan, additional, Brandsma, Corry-Anke, additional, Chen, Zhengming, additional, Crapo, James D, additional, Danesh, John, additional, DeMeo, Dawn L, additional, Dudbridge, Frank, additional, Ewert, Ralf, additional, Gieger, Christian, additional, Gulsvik, Amund, additional, Hansell, Anna L, additional, Hao, Ke, additional, Hoffman, Josh D, additional, Hokanson, John, additional, Homuth, Georg, additional, Joshi, Peter K, additional, Joubert, Philippe, additional, Langenberg, Claudia, additional, Li, Xuan, additional, Li, Liming, additional, Lin, Kuang, additional, Lind, Lars, additional, Locantore, Nick, additional, Luan, Jian’an, additional, Mahajan, Anubha, additional, Maranville, Joseph C, additional, Murray, Alison, additional, Nickle, David C, additional, Packer, Richard, additional, Parker, Margaret M, additional, Paynton, Megan L, additional, Porteous, David, additional, Prokopenko, Dmitry, additional, Qiao, Dandi, additional, Rawal, Rajesh, additional, Runz, Heiko, additional, Sayers, Ian, additional, Sin, Don D, additional, H Smith, Blair, additional, Artigas, María Soler, additional, Sparrow, David, additional, Tal-Singer, Ruth, additional, Timmers, Paul RHJ, additional, Van den Berge, Maarten, additional, Whittaker, John C, additional, Woodruff, Prescott, additional, M Yerges Armstrong, Laura, additional, Troyanskaya, Olga G, additional, Raitakari, Olli T, additional, Kähönen, Mika, additional, Polasek, Ozren, additional, Gyllensten, Ulf, additional, Rudan, Igor, additional, Deary, Ian J, additional, Probst-Hensch, Nicole M, additional, Schulz, Holger, additional, James, Alan L, additional, Wilson, James F, additional, Stubbe, Beate, additional, Zeggini, Eleftheria, additional, Jarvelin, Marjo-Riitta, additional, Wareham, Nick, additional, Silverman, Edwin K, additional, Hayward, Caroline, additional, Morris, Andrew P, additional, Butterworth, Adam S, additional, Scott, Robert A, additional, Walters, Robin G, additional, Meyers, Deborah A, additional, Cho, Michael H, additional, Strachan, David P, additional, Hall, Ian P, additional, Tobin, Martin D, additional, and Wain, Louise V, additional

Published
2018
Full Text
View/download PDF

47. Meta-analysis of exome array data identifies six novel genetic loci for lung function.

Author

Jackson, Victoria E, Latourelle, Jeanne C, Wain, Louise V, Smith, Albert V, Grove, Megan L, Bartz, Traci M, Obeidat, Ma'en, Province, Michael A, Gao, Wei, Qaiser, Beenish, Porteous, David J, Cassano, Patricia A, Ahluwalia, Tarunveer S, Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E, Manichaikul, Ani, Pottinger, Tess D, Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo-Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M, Brody, Jennifer A, Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M, Linneberg, Allan, Lange, Leslie A, Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E, Smith, Blair H, Davies, Gail, Burkart, Kristin M, Mychaleckyj, Josyf C, Bonten, Tobias N, Enroth, Stefan, Lind, Lars, Brusselle, Guy G, Kumar, Ashish, Stubbe, Beate, Kähönen, Mika, Wyss, Annah B, Psaty, Bruce M, Heckbert, Susan R, Hao, Ke, Rantanen, Taina, Kritchevsky, Stephen B, Lohman, Kurt, Skaaby, Tea, Pisinger, Charlotta, Hansen, Torben, Schulz, Holger, Polasek, Ozren, Campbell, Archie, Starr, John M, Rich, Stephen S, Mook-Kanamori, Dennis O, Johansson, Åsa, Ingelsson, Erik, Uitterlinden, André G, Weiss, Stefan, Raitakari, Olli T, Gudnason, Vilmundur, North, Kari E, Gharib, Sina A, Sin, Don D, Taylor, Kent D, O'Connor, George T, Kaprio, Jaakko, Harris, Tamara B, Pederson, Oluf, Vestergaard, Henrik, Wilson, James G, Strauch, Konstantin, Hayward, Caroline, Kerr, Shona, Deary, Ian J, Barr, R Graham, de Mutsert, Renée, Gyllensten, Ulf, Morris, Andrew P, Ikram, M Arfan, Probst-Hensch, Nicole, Gläser, Sven, Zeggini, Eleftheria, Lehtimäki, Terho, Strachan, David P, Dupuis, Josée, Morrison, Alanna C, Hall, Ian P, Tobin, Martin D, London, Stephanie J, Jackson, Victoria E, Latourelle, Jeanne C, Wain, Louise V, Smith, Albert V, Grove, Megan L, Bartz, Traci M, Obeidat, Ma'en, Province, Michael A, Gao, Wei, Qaiser, Beenish, Porteous, David J, Cassano, Patricia A, Ahluwalia, Tarunveer S, Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E, Manichaikul, Ani, Pottinger, Tess D, Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo-Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M, Brody, Jennifer A, Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M, Linneberg, Allan, Lange, Leslie A, Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E, Smith, Blair H, Davies, Gail, Burkart, Kristin M, Mychaleckyj, Josyf C, Bonten, Tobias N, Enroth, Stefan, Lind, Lars, Brusselle, Guy G, Kumar, Ashish, Stubbe, Beate, Kähönen, Mika, Wyss, Annah B, Psaty, Bruce M, Heckbert, Susan R, Hao, Ke, Rantanen, Taina, Kritchevsky, Stephen B, Lohman, Kurt, Skaaby, Tea, Pisinger, Charlotta, Hansen, Torben, Schulz, Holger, Polasek, Ozren, Campbell, Archie, Starr, John M, Rich, Stephen S, Mook-Kanamori, Dennis O, Johansson, Åsa, Ingelsson, Erik, Uitterlinden, André G, Weiss, Stefan, Raitakari, Olli T, Gudnason, Vilmundur, North, Kari E, Gharib, Sina A, Sin, Don D, Taylor, Kent D, O'Connor, George T, Kaprio, Jaakko, Harris, Tamara B, Pederson, Oluf, Vestergaard, Henrik, Wilson, James G, Strauch, Konstantin, Hayward, Caroline, Kerr, Shona, Deary, Ian J, Barr, R Graham, de Mutsert, Renée, Gyllensten, Ulf, Morris, Andrew P, Ikram, M Arfan, Probst-Hensch, Nicole, Gläser, Sven, Zeggini, Eleftheria, Lehtimäki, Terho, Strachan, David P, Dupuis, Josée, Morrison, Alanna C, Hall, Ian P, Tobin, Martin D, and London, Stephanie J

Abstract

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

Published
2018
Full Text
View/download PDF

48. Meta-analysis of exome array data identifies six novel genetic loci for lung function [version 1; peer review:1 approved, 1 approved with reservations]

Author

Jackson, Victoria E., Latourelle, Jeanne C., Wain, Louise V., Smith, Albert V., Grove, Megan L., Bartz, Traci M., Obeidat, Ma’En, Province, Michael A., Gao, Wei, Qaiser, Beenish, Porteous, David J., Cassano, Patricia A., Ahluwalia, Tarunveer S., Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E., Manichaikul, Ani, Pottinger, Tess D., Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M., Brody, Jennifer A., Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M., Linneberg, Allan, Lange, Leslie A., Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E., Brusselle, Guy G., Hansen, Torben, Uitterlinden, André G., Ikram, M. Arfan, Dupuis, Josée, Jackson, Victoria E., Latourelle, Jeanne C., Wain, Louise V., Smith, Albert V., Grove, Megan L., Bartz, Traci M., Obeidat, Ma’En, Province, Michael A., Gao, Wei, Qaiser, Beenish, Porteous, David J., Cassano, Patricia A., Ahluwalia, Tarunveer S., Grarup, Niels, Li, Jin, Altmaier, Elisabeth, Marten, Jonathan, Harris, Sarah E., Manichaikul, Ani, Pottinger, Tess D., Li-Gao, Ruifang, Lind-Thomsen, Allan, Mahajan, Anubha, Lahousse, Lies, Imboden, Medea, Teumer, Alexander, Prins, Bram, Lyytikäinen, Leo Pekka, Eiriksdottir, Gudny, Franceschini, Nora, Sitlani, Colleen M., Brody, Jennifer A., Bossé, Yohan, Timens, Wim, Kraja, Aldi, Loukola, Anu, Tang, Wenbo, Liu, Yongmei, Bork-Jensen, Jette, Justesen, Johanne M., Linneberg, Allan, Lange, Leslie A., Rawal, Rajesh, Karrasch, Stefan, Huffman, Jennifer E., Brusselle, Guy G., Hansen, Torben, Uitterlinden, André G., Ikram, M. Arfan, and Dupuis, Josée

Abstract

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2•8x10 -7 ) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

Published
2018

49. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Author

Wyss, Annah B., Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N., Lahousse, Lies, Latourelle, Jeanne C., Smith, Albert Vernon, Bartz, Traci M., Feitosa, Mary F., Gao, Wei, Ahluwalia, Tarunveer S., Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K., Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E., Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D., Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M., Hu, Donglei, Mogil, Lauren S., Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B., Kalhan, Ravi, Heckbert, Susan R., Paternoster, Lavinia, Burkart, Kristin M., Liu, Yongmei, Holliday, Elizabeth G., Wilson, James G., Vonk, Judith M., Sanders, Jason L., Barr, R. Graham, de Mutsert, Renee, Baptista Menezes, Ana Maria, Adams, Hieab H. H., van den Berge, Maarten, Joehanes, Roby, Levin, Albert M., Liberto, Jennifer, Launer, Lenore J., Morrison, Alanna C., Sitlani, Colleen M., Celedon, Juan C., Kritchevsky, Stephen B., Scott, Rodney J., Christensen, Kaare, Rotter, Jerome I., Bonten, Tobias N., Wehrmeister, Fernando Cesar, Bosse, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A., Kaplan, Robert C., Lohman, Kurt, McEvoy, Mark, Province, Michael A., Rosendaal, Frits R., Taylor, Kent D., Nickle, David C., Williams, L. Keoki, Burchard, Esteban G., Wheeler, Heather E., Sin, Don D., Gudnason, Vilmundur, North, Kari E., Fornage, Myriam, Psaty, Bruce M., Myers, Richard H., O'Connor, George, Hansen, Torben, Laurie, Cathy C., Cassano, Patricia A., Sung, Joohon, Kim, Woo Jin, Attia, John R., Lange, Leslie, Boezen, H. Marike, Thyagarajan, Bharat, Rich, Stephen S., Mook-Kanamori, Dennis O., Horta, Bernardo Lessa, Uitterlinden, Andre G., Im, Hae Kyung, Cho, Michael H., Brusselle, Guy G., Gharib, Sina A., Dupuis, Josee, Manichaikul, Ani, London, Stephanie J., Wyss, Annah B., Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N., Lahousse, Lies, Latourelle, Jeanne C., Smith, Albert Vernon, Bartz, Traci M., Feitosa, Mary F., Gao, Wei, Ahluwalia, Tarunveer S., Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K., Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E., Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D., Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M., Hu, Donglei, Mogil, Lauren S., Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B., Kalhan, Ravi, Heckbert, Susan R., Paternoster, Lavinia, Burkart, Kristin M., Liu, Yongmei, Holliday, Elizabeth G., Wilson, James G., Vonk, Judith M., Sanders, Jason L., Barr, R. Graham, de Mutsert, Renee, Baptista Menezes, Ana Maria, Adams, Hieab H. H., van den Berge, Maarten, Joehanes, Roby, Levin, Albert M., Liberto, Jennifer, Launer, Lenore J., Morrison, Alanna C., Sitlani, Colleen M., Celedon, Juan C., Kritchevsky, Stephen B., Scott, Rodney J., Christensen, Kaare, Rotter, Jerome I., Bonten, Tobias N., Wehrmeister, Fernando Cesar, Bosse, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A., Kaplan, Robert C., Lohman, Kurt, McEvoy, Mark, Province, Michael A., Rosendaal, Frits R., Taylor, Kent D., Nickle, David C., Williams, L. Keoki, Burchard, Esteban G., Wheeler, Heather E., Sin, Don D., Gudnason, Vilmundur, North, Kari E., Fornage, Myriam, Psaty, Bruce M., Myers, Richard H., O'Connor, George, Hansen, Torben, Laurie, Cathy C., Cassano, Patricia A., Sung, Joohon, Kim, Woo Jin, Attia, John R., Lange, Leslie, Boezen, H. Marike, Thyagarajan, Bharat, Rich, Stephen S., Mook-Kanamori, Dennis O., Horta, Bernardo Lessa, Uitterlinden, Andre G., Im, Hae Kyung, Cho, Michael H., Brusselle, Guy G., Gharib, Sina A., Dupuis, Josee, Manichaikul, Ani, and London, Stephanie J.

Published
2018

50. 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
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results