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2. Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma

Author

Porsbjerg, Celeste M., Menzies-Gow, Andrew N., Tran, Trung N., Murray, Ruth B., Unni, Bindhu, Audrey Ang, Shi Ling, Alacqua, Marianna, Al-Ahmad, Mona, Al-Lehebi, Riyad, Altraja, Alan, Belevskiy, Andrey S., Björnsdóttir, Unnur S., Bourdin, Arnaud, Busby, John, Canonica, G. Walter, Christoff, George C., Cosio, Borja G., Costello, Richard W., FitzGerald, J. Mark, Fonseca, João A., Hansen, Susanne, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Iwanaga, Takashi, Jackson, David J., Kocks, Janwillem W.H., Kallieri, Maria, Bruce Ko, Hsin-Kuo, Koh, Mariko Siyue, Larenas-Linnemann, Désirée, Lehtimäki, Lauri A., Loukides, Stelios, Lugogo, Njira, Maspero, Jorge, Papaioannou, Andriana I., Perez-de-Llano, Luis, Pitrez, Paulo Márcio, Popov, Todor A., Rasmussen, Linda M., Rhee, Chin Kook, Sadatsafavi, Mohsen, Schmid, Johannes, Siddiqui, Salman, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte, Upham, John W., Wang, Eileen, Wechsler, Michael E., Bulathsinhala, Lakmini, Carter, Victoria, Chaudhry, Isha, Eleangovan, Neva, Hosseini, Naeimeh, Rowlands, Mari-Anne, Price, David B., and van Boven, Job F.M.

Published
2022
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3. Real World Biologic Use and Switch Patterns in Severe Asthma: Data from the International Severe Asthma Registry and the US CHRONICLE Study

Author

Menzies-Gow, Andrew N. McBrien, Claire Unni, Bindhu and Porsbjerg, Celeste M. Al-Ahmad, Mona Ambrose, Christopher S. and Assing, Karin Dahl von Bulow, Anna Busby, John Cosio, Borja G. FitzGerald, J. Mark Gil, Esther Garcia Hansen, Susanne and aHeaney, Liam G. Hew, Mark Jackson, David J. Kallieri, Maria Loukides, Stelios Lugogo, Njira L. Papaioannou, I, Andriana Larenas-Linnemann, Desiree Moore, Wendy C. and Perez-de-Llano, Luis A. Rasmussen, Linda M. Schmid, Johannes M. and Siddiqui, Salman Alacqua, Marianna Tran, Trung N. Ulrik, Charlotte Suppli Upham, John W. Wang, Elleen Bulathsinhala, Lakmini Carter, Victoria A. Chaudhry, Isha Eleangovan, Neva and Murray, Ruth B. Price, Chris A. Price, David B. and Menzies-Gow, Andrew N. McBrien, Claire Unni, Bindhu and Porsbjerg, Celeste M. Al-Ahmad, Mona Ambrose, Christopher S. and Assing, Karin Dahl von Bulow, Anna Busby, John Cosio, Borja G. FitzGerald, J. Mark Gil, Esther Garcia Hansen, Susanne and aHeaney, Liam G. Hew, Mark Jackson, David J. Kallieri, Maria Loukides, Stelios Lugogo, Njira L. Papaioannou, I, Andriana Larenas-Linnemann, Desiree Moore, Wendy C. and Perez-de-Llano, Luis A. Rasmussen, Linda M. Schmid, Johannes M. and Siddiqui, Salman Alacqua, Marianna Tran, Trung N. Ulrik, Charlotte Suppli Upham, John W. Wang, Elleen Bulathsinhala, Lakmini Carter, Victoria A. Chaudhry, Isha Eleangovan, Neva and Murray, Ruth B. Price, Chris A. Price, David B.

Abstract

Introduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors. Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015-2020) or the CHRONICLE Study (2018-2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups. Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti-IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti-IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization. Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.

Published
2022

4. Real World Biologic Use and Switch Patterns in Severe Asthma: Data from the International Severe Asthma Registry and the US CHRONICLE Study

Author

Menzies-Gow,Andrew N, McBrien,Claire, Unni,Bindhu, Porsbjerg,Celeste M, Al-Ahmad,Mona, Ambrose,Christopher S, Dahl Assing,Karin, von Bülow,Anna, Busby,John, Cosio,Borja G, FitzGerald,J Mark, Garcia Gil,Esther, Hansen,Susanne, Heaney,Liam G, Hew,Mark, Jackson,David J, Kallieri,Maria, Loukides,Stelios, Lugogo,Njira L, Papaioannou,Andriana I, Larenas-Linnemann,Désirée, Moore,Wendy C, Perez-de-Llano,Luis A, Rasmussen,Linda M, Schmid,Johannes M, Siddiqui,Salman, Alacqua,Marianna, Tran,Trung N, Suppli Ulrik,Charlotte, Upham,John W, Wang,Eileen, Bulathsinhala,Lakmini, Carter,Victoria A, Chaudhry,Isha, Eleangovan,Neva, Murray,Ruth B, Price,Chris A, Price,David B, Menzies-Gow,Andrew N, McBrien,Claire, Unni,Bindhu, Porsbjerg,Celeste M, Al-Ahmad,Mona, Ambrose,Christopher S, Dahl Assing,Karin, von Bülow,Anna, Busby,John, Cosio,Borja G, FitzGerald,J Mark, Garcia Gil,Esther, Hansen,Susanne, Heaney,Liam G, Hew,Mark, Jackson,David J, Kallieri,Maria, Loukides,Stelios, Lugogo,Njira L, Papaioannou,Andriana I, Larenas-Linnemann,Désirée, Moore,Wendy C, Perez-de-Llano,Luis A, Rasmussen,Linda M, Schmid,Johannes M, Siddiqui,Salman, Alacqua,Marianna, Tran,Trung N, Suppli Ulrik,Charlotte, Upham,John W, Wang,Eileen, Bulathsinhala,Lakmini, Carter,Victoria A, Chaudhry,Isha, Eleangovan,Neva, Murray,Ruth B, Price,Chris A, and Price,David B

Abstract

Andrew N Menzies-Gow,1 Claire McBrien,2 Bindhu Unni,3 Celeste M Porsbjerg,4 Mona Al-Ahmad,5 Christopher S Ambrose,6 Karin Dahl Assing,7 Anna von Bülow,4 John Busby,8 Borja G Cosio,9 J Mark FitzGerald,10 Esther Garcia Gil,11 Susanne Hansen,12 Liam G aHeaney,8 Mark Hew,13,14 David J Jackson,15,16 Maria Kallieri,17 Stelios Loukides,17 Njira L Lugogo,18 Andriana I Papaioannou,17 Désirée Larenas-Linnemann,19 Wendy C Moore,20 Luis A Perez-de-Llano,21 Linda M Rasmussen,22 Johannes M Schmid,23 Salman Siddiqui,24 Marianna Alacqua,25 Trung N Tran,6 Charlotte Suppli Ulrik,26 John W Upham,27 Eileen Wang,28,29 Lakmini Bulathsinhala,3,30 Victoria A Carter,3,30 Isha Chaudhry,3,30 Neva Eleangovan,3,30 Ruth B Murray,3,30 Chris A Price,3,30 David B Price3,30,31 1UK Severe Asthma Network and National Registry, Royal Brompton & Harefield Hospitals, London, UK; 2Kingston Hospital, London, UK; 3Observational and Pragmatic Research Institute, Singapore, Singapore; 4Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 5Al-Rashed Allergy Center, Ministry of Health, Microbiology Department, Faculty of Medicine, Kuwait University, Kuwait, Kuwait; 6AstraZeneca, Gaithersburg, MD, USA; 7Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 8UK Severe Asthma Network and National Registry, Queen’s University Belfast, Belfast, Northern Ireland; 9Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 10The Centre for Lung Health, Vancouver Coastal Health Research Institute, UBC, Vancouver, Canada; 11AstraZeneca, Barcelona, Spain; 12Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 13Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; 14Public Health and Preventive Medicine, Monash University, Melbourne, Australia; 15UK Severe Asthma Network andNational Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 16School of Immunology &amp

Published
2022

5. Real World Biologic Use and Switch Patterns in Severe Asthma:Data from the International Severe Asthma Registry and the US CHRONICLE Study

Author

Menzies-Gow, Andrew N., McBrien, Claire, Unni, Bindhu, Porsbjerg, Celeste M., Al-Ahmad, Mona, Ambrose, Christopher S., Dahl Assing, Karin, von Bülow, Anna, Busby, John, Cosio, Borja G., Fitzgerald, J. Mark, Garcia Gil, Esther, Hansen, Susanne, Aheaney, Liam G., Hew, Mark, Jackson, David J., Kallieri, Maria, Loukides, Stelios, Lugogo, Njira L., Papaioannou, Andriana I., Larenas-Linnemann, Désirée, Moore, Wendy C., Perez-De-llano, Luis A., Rasmussen, Linda M., Schmid, Johannes M., Siddiqui, Salman, Alacqua, Marianna, Tran, Trung N., Suppli Ulrik, Charlotte, Upham, John W., Wang, Eileen, Bulathsinhala, Lakmini, Carter, Victoria A., Chaudhry, Isha, Eleangovan, Neva, Murray, Ruth B., Price, Chris A., Price, David B., Menzies-Gow, Andrew N., McBrien, Claire, Unni, Bindhu, Porsbjerg, Celeste M., Al-Ahmad, Mona, Ambrose, Christopher S., Dahl Assing, Karin, von Bülow, Anna, Busby, John, Cosio, Borja G., Fitzgerald, J. Mark, Garcia Gil, Esther, Hansen, Susanne, Aheaney, Liam G., Hew, Mark, Jackson, David J., Kallieri, Maria, Loukides, Stelios, Lugogo, Njira L., Papaioannou, Andriana I., Larenas-Linnemann, Désirée, Moore, Wendy C., Perez-De-llano, Luis A., Rasmussen, Linda M., Schmid, Johannes M., Siddiqui, Salman, Alacqua, Marianna, Tran, Trung N., Suppli Ulrik, Charlotte, Upham, John W., Wang, Eileen, Bulathsinhala, Lakmini, Carter, Victoria A., Chaudhry, Isha, Eleangovan, Neva, Murray, Ruth B., Price, Chris A., and Price, David B.

Abstract

Introduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors. Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015–2020) or the CHRONICLE Study (2018–2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/ switching were recorded and comparisons drawn between groups. Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti–IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti–IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization. Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.

Published
2022

6. Real World Biologic Use and Switch Patterns in Severe Asthma: Data from the International Severe Asthma Registry and the US CHRONICLE Study

Author

Menzies-Gow, Andrew N, primary, McBrien, Claire, additional, Unni, Bindhu, additional, Porsbjerg, Celeste M, additional, Al-Ahmad, Mona, additional, Ambrose, Christopher S, additional, Dahl Assing, Karin, additional, von Bülow, Anna, additional, Busby, John, additional, Cosio, Borja G, additional, FitzGerald, J Mark, additional, Garcia Gil, Esther, additional, Hansen, Susanne, additional, Heaney, Liam G, additional, Hew, Mark, additional, Jackson, David J, additional, Kallieri, Maria, additional, Loukides, Stelios, additional, Lugogo, Njira L, additional, Papaioannou, Andriana I, additional, Larenas-Linnemann, Désirée, additional, Moore, Wendy C, additional, Perez-de-Llano, Luis A, additional, Rasmussen, Linda M, additional, Schmid, Johannes M, additional, Siddiqui, Salman, additional, Alacqua, Marianna, additional, Tran, Trung N, additional, Suppli Ulrik, Charlotte, additional, Upham, John W, additional, Wang, Eileen, additional, Bulathsinhala, Lakmini, additional, Carter, Victoria A, additional, Chaudhry, Isha, additional, Eleangovan, Neva, additional, Murray, Ruth B, additional, Price, Chris A, additional, and Price, David B, additional

Published
2022
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8. YKL-40 and genetic status of CHI3L1 in a large group of asthmatics

Author

Hansen, Jakob W, Thomsen, Simon F, Porsbjerg, Celeste, Rasmussen, Linda M, Harmsen, Lotte, Johansen, Julia S, Backer, Vibeke, Hansen, Jakob W, Thomsen, Simon F, Porsbjerg, Celeste, Rasmussen, Linda M, Harmsen, Lotte, Johansen, Julia S, and Backer, Vibeke

Abstract

BACKGROUND: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40, and SNP (-131 C/G, rs4950928).METHODS: In this study, 1,137 patients with asthma, 415 with rhinitis only, and 275 non-asthmatic controls were included. Assessment included a clinical interview concerning the diagnosis of asthma, severity of asthma, and asthma treatment as well as clinical tests to assess asthma and rhinitis. Serum YKL-40 was measured, and genotyping for the SNP (-131 C/G) was conducted.RESULTS: No significant difference in the serum concentration of YKL-40 was found between patients with asthma, patients with rhinitis, and non-asthmatic controls; however, YKL-40 was increased in patients with severe asthma. No association was found between the SNP (-131 C/G rs4950982) and the risk of having asthma (odds ratio = 0.90, p=0.4). Higher levels of serum YKL-40 were found in all subjects when comparing CC genotype to CG and GG genotypes (45 µg/L vs. 32 µg/L and 19 µg/L, p<0.0001).CONCLUSION: There was no association between polymorphisms of SNP (-131 C/G) and asthma. The highest serum YKL-40 concentrations were seen in severe asthmatics. Individuals with less severe asthma showed a smaller difference against controls, limiting its clinical usefulness. More research is needed to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1.

Published
2015

10. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Author

Gudbjartsson, Daniel F., Bjornsdottir, Unnur S., Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M., Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M., James, Alan, Palmer, Lyle J., Koppelman, Gerard H., Heinzmann, Andrea, Krueger, Marcus, Boezen, H. Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M., Porsbjerg, Celeste, Hansen, Jakob W., Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C. Y., Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Levey, Allan I., Vaccarino, Viola, Reilly, Muredach P., Rader, Daniel J., Williams, Michael J. A., van Rij, Andre M., Jones, Gregory T., Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R., Ludviksdottir, Dora, Eyjolfsson, Gudmundur I., Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J., Wjst, Matthias, Hall, Ian P., Postma, Dirkje S., Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Stefansson, Kari, Gudbjartsson, Daniel F., Bjornsdottir, Unnur S., Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M., Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M., James, Alan, Palmer, Lyle J., Koppelman, Gerard H., Heinzmann, Andrea, Krueger, Marcus, Boezen, H. Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M., Porsbjerg, Celeste, Hansen, Jakob W., Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C. Y., Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Levey, Allan I., Vaccarino, Viola, Reilly, Muredach P., Rader, Daniel J., Williams, Michael J. A., van Rij, Andre M., Jones, Gregory T., Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R., Ludviksdottir, Dora, Eyjolfsson, Gudmundur I., Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J., Wjst, Matthias, Hall, Ian P., Postma, Dirkje S., Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, and Stefansson, Kari

Abstract

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Published
2009
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11. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Author

Gudbjartsson, Daniel F, Bjornsdottir, Unnur S, Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M, Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M, James, Alan, Palmer, Lyle J, Koppelman, Gerard H, Heinzmann, Andrea, Krueger, Marcus, Boezen, H Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M, Porsbjerg, Celeste, Hansen, Jakob W, Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C Y, Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Levey, Allan I, Vaccarino, Viola, Reilly, Muredach P, Rader, Daniel J, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R, Ludviksdottir, Dora, Eyjolfsson, Gudmundur I, Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J, Wjst, Matthias, Hall, Ian P, Postma, Dirkje S, Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Stefansson, Kari, Gudbjartsson, Daniel F, Bjornsdottir, Unnur S, Halapi, Eva, Helgadottir, Anna, Sulem, Patrick, Jonsdottir, Gudrun M, Thorleifsson, Gudmar, Helgadottir, Hafdis, Steinthorsdottir, Valgerdur, Stefansson, Hreinn, Williams, Carolyn, Hui, Jennie, Beilby, John, Warrington, Nicole M, James, Alan, Palmer, Lyle J, Koppelman, Gerard H, Heinzmann, Andrea, Krueger, Marcus, Boezen, H Marike, Wheatley, Amanda, Altmuller, Janine, Shin, Hyoung Doo, Uh, Soo-Taek, Cheong, Hyun Sub, Jonsdottir, Brynja, Gislason, David, Park, Choon-Sik, Rasmussen, Linda M, Porsbjerg, Celeste, Hansen, Jakob W, Backer, Vibeke, Werge, Thomas, Janson, Christer, Jönsson, Ulla-Britt, Ng, Maggie C Y, Chan, Juliana, So, Wing Yee, Ma, Ronald, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Levey, Allan I, Vaccarino, Viola, Reilly, Muredach P, Rader, Daniel J, Williams, Michael J A, van Rij, Andre M, Jones, Gregory T, Trabetti, Elisabetta, Malerba, Giovanni, Pignatti, Pier Franco, Boner, Attilio, Pescollderungg, Lydia, Girelli, Domenico, Olivieri, Oliviero, Martinelli, Nicola, Ludviksson, Bjorn R, Ludviksdottir, Dora, Eyjolfsson, Gudmundur I, Arnar, David, Thorgeirsson, Gudmundur, Deichmann, Klaus, Thompson, Philip J, Wjst, Matthias, Hall, Ian P, Postma, Dirkje S, Gislason, Thorarinn, Gulcher, Jeffrey, Kong, Augustine, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, and Stefansson, Kari

Abstract

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Published
2009

12. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Author

Gudbjartsson, Daniel F, primary, Bjornsdottir, Unnur S, additional, Halapi, Eva, additional, Helgadottir, Anna, additional, Sulem, Patrick, additional, Jonsdottir, Gudrun M, additional, Thorleifsson, Gudmar, additional, Helgadottir, Hafdis, additional, Steinthorsdottir, Valgerdur, additional, Stefansson, Hreinn, additional, Williams, Carolyn, additional, Hui, Jennie, additional, Beilby, John, additional, Warrington, Nicole M, additional, James, Alan, additional, Palmer, Lyle J, additional, Koppelman, Gerard H, additional, Heinzmann, Andrea, additional, Krueger, Marcus, additional, Boezen, H Marike, additional, Wheatley, Amanda, additional, Altmuller, Janine, additional, Shin, Hyoung Doo, additional, Uh, Soo-Taek, additional, Cheong, Hyun Sub, additional, Jonsdottir, Brynja, additional, Gislason, David, additional, Park, Choon-Sik, additional, Rasmussen, Linda M, additional, Porsbjerg, Celeste, additional, Hansen, Jakob W, additional, Backer, Vibeke, additional, Werge, Thomas, additional, Janson, Christer, additional, Jönsson, Ulla-Britt, additional, Ng, Maggie C Y, additional, Chan, Juliana, additional, So, Wing Yee, additional, Ma, Ronald, additional, Shah, Svati H, additional, Granger, Christopher B, additional, Quyyumi, Arshed A, additional, Levey, Allan I, additional, Vaccarino, Viola, additional, Reilly, Muredach P, additional, Rader, Daniel J, additional, Williams, Michael J A, additional, van Rij, Andre M, additional, Jones, Gregory T, additional, Trabetti, Elisabetta, additional, Malerba, Giovanni, additional, Pignatti, Pier Franco, additional, Boner, Attilio, additional, Pescollderungg, Lydia, additional, Girelli, Domenico, additional, Olivieri, Oliviero, additional, Martinelli, Nicola, additional, Ludviksson, Bjorn R, additional, Ludviksdottir, Dora, additional, Eyjolfsson, Gudmundur I, additional, Arnar, David, additional, Thorgeirsson, Gudmundur, additional, Deichmann, Klaus, additional, Thompson, Philip J, additional, Wjst, Matthias, additional, Hall, Ian P, additional, Postma, Dirkje S, additional, Gislason, Thorarinn, additional, Gulcher, Jeffrey, additional, Kong, Augustine, additional, Jonsdottir, Ingileif, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2009
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