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719 results on '"Løset, A"'

2. A genome-wide meta-analysis of palmoplantar pustulosis implicates TH2 responses and cigarette smoking in disease pathogenesis

Author

Abraham, Thamir, Ali, Muhmad, August, Suzannah, Baudry, David, Becher, Gabrielle, Bewley, Anthony, Brown, Victoria, Cornelius, Victoria, Ghaffar, Sharizan, Ingram, John, Kavakleiva, Svetlana, Kelly, Susan, Khorshid, Mohsen, Lachmann, Helen, Ladoyanni, Effie, McAteer, Helen, McKenna, John, Meynell, Freya, Patel, Prakash, Pink, Andrew, Powell, Kingsley, Pushparajah, Angela, Sinclair, Catriona, Wachsmuth, Rachel, Hernandez-Cordero, Ariana, Thomas, Laurent, Smail, Alice, Lim, Zhao Qin, Saklatvala, Jake R., Chung, Raymond, Curtis, Charles J., Baum, Patrick, Visvanathan, Sudha, Burden, A. David, Cooper, Hywel L., Dunnill, Giles, Griffiths, Christopher E.M., Levell, Nick J., Parslew, Richard, Reynolds, Nick J., Wahie, Shyamal, Warren, Richard B., Wright, Andrew, Simpson, Michael, Hveem, Kristian, Barker, Jonathan N., Dand, Nick, Løset, Mari, Smith, Catherine H., and Capon, Francesca

Published
2024
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4. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Author

Ashley Budu-Aggrey, Anna Kilanowski, Maria K. Sobczyk, andMe Research Team, Suyash S. Shringarpure, Ruth Mitchell, Kadri Reis, Anu Reigo, Estonian Biobank Research Team, Reedik Mägi, Mari Nelis, Nao Tanaka, Ben M. Brumpton, Laurent F. Thomas, Pol Sole-Navais, Christopher Flatley, Antonio Espuela-Ortiz, Esther Herrera-Luis, Jesus V. T. Lominchar, Jette Bork-Jensen, Ingo Marenholz, Aleix Arnau-Soler, Ayoung Jeong, Katherine A. Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M. Sleiman, Xiao Chang, Carolina Medina-Gomez, Chen Hu, Cheng-jian Xu, Cancan Qi, Sarah El-Heis, Philip Titcombe, Elie Antoun, João Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas Hoffmann, Eric Jorgenson, Hélène Choquet, Neil Risch, Pål Njølstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K. E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line L. Kårhus, Thomas M. Dantoft, Alexander C.S.N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Nöthen, Norbert Hübner, Medea Imboden, Alessia Visconti, Mario Falchi, Veronique Bataille, Pirro Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke J. Hottenga, Martina Müller-Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann-Marie M. Schoos, Ana Esplugues, Mariona Bustamante, Benjamin Raby, Syed Arshad, Chris German, Tõnu Esko, Lili A. Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Løset, Kristian Hveem, Bo Jacobsson, Maria Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young-Ae Lee, Nicole Probst-Hensch, Stephan Weidinger, Marjo-Riitta Jarvelin, Erik Melén, Hakon Hakonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bønnelykke, John Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara J. Brown, Marie Standl, and Lavinia Paternoster

Subjects
Science
Abstract

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

Published
2023
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5. Chimeric antigen receptor T cells targeting the GM3(Neu5Gc) ganglioside

Author

Julia Heinzelbecker, Marte Fauskanger, Ida Jonson, Ute Krengel, Geir Åge Løset, Ludvig Munthe, and Anders Tveita

Subjects
CAR (chimeric antigen receptor) T cells, GM3(Neu5Gc) ganglioside, carbohydrate antigen, solid tumor, immunotherapy, 14F7, Immunologic diseases. Allergy, RC581-607
Abstract

Chimeric antigen receptor (CAR) T cell technology has ushered in a new era of immunotherapy, enabling the targeting of a broad range of surface antigens, surpassing the limitations of traditional T cell epitopes. Despite the wide range of non-protein tumor-associated antigens, the advancement in crafting CAR T cells for these targets has been limited. Owing to an evolutionary defect in the CMP-Neu5Ac hydroxylase (CMAH) that abolishes the synthesis of CMP-Neu5Gc from CMP-Neu5Ac, Neu5Gc is generally absent in human tissues. Despite this, Neu5Gc-containing antigens, including the ganglioside GM3(Neu5Gc) have consistently been observed on tumor cells across a variety of human malignancies. This restricted expression makes GM3(Neu5Gc) an appealing and highly specific target for immunotherapy. In this study, we designed and evaluated 14F7-28z CAR T cells, with a targeting unit derived from the GM3(Neu5Gc)-specific murine antibody 14F7. These cells exhibited exceptional specificity, proficiently targeting GM3(Neu5Gc)-expressing murine tumor cells in syngeneic mouse models, ranging from B cell malignancies to epithelial tumors, without compromising safety. Notably, human tumor cells enhanced with murine Cmah were effectively targeted and eliminated by the 14F7 CAR T cells. Nonetheless, despite the detectable presence of GM3(Neu5Gc) in unmodified human tumor xenografts, the levels were insufficient to trigger a tumoricidal T-cell response with the current CAR T cell configuration. Overall, our findings highlight the potential of targeting the GM3(Neu5Gc) ganglioside using CAR T cells across a variety of cancers and set the stage for the optimization of 14F7-based therapies for future human clinical application.

Published
2024
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6. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Author

Budu-Aggrey, Ashley, Kilanowski, Anna, Sobczyk, Maria K., Shringarpure, Suyash S., Mitchell, Ruth, Reis, Kadri, Reigo, Anu, Mägi, Reedik, Nelis, Mari, Tanaka, Nao, Brumpton, Ben M., Thomas, Laurent F., Sole-Navais, Pol, Flatley, Christopher, Espuela-Ortiz, Antonio, Herrera-Luis, Esther, Lominchar, Jesus V. T., Bork-Jensen, Jette, Marenholz, Ingo, Arnau-Soler, Aleix, Jeong, Ayoung, Fawcett, Katherine A., Baurecht, Hansjorg, Rodriguez, Elke, Alves, Alexessander Couto, Kumar, Ashish, Sleiman, Patrick M., Chang, Xiao, Medina-Gomez, Carolina, Hu, Chen, Xu, Cheng-jian, Qi, Cancan, El-Heis, Sarah, Titcombe, Philip, Antoun, Elie, Fadista, João, Wang, Carol A., Thiering, Elisabeth, Wu, Baojun, Kress, Sara, Kothalawala, Dilini M., Kadalayil, Latha, Duan, Jiasong, Zhang, Hongmei, Hadebe, Sabelo, Hoffmann, Thomas, Jorgenson, Eric, Choquet, Hélène, Risch, Neil, Njølstad, Pål, Andreassen, Ole A., Johansson, Stefan, Almqvist, Catarina, Gong, Tong, Ullemar, Vilhelmina, Karlsson, Robert, Magnusson, Patrik K. E., Szwajda, Agnieszka, Burchard, Esteban G., Thyssen, Jacob P., Hansen, Torben, Kårhus, Line L., Dantoft, Thomas M., Jeanrenaud, Alexander C.S.N., Ghauri, Ahla, Arnold, Andreas, Homuth, Georg, Lau, Susanne, Nöthen, Markus M., Hübner, Norbert, Imboden, Medea, Visconti, Alessia, Falchi, Mario, Bataille, Veronique, Hysi, Pirro, Ballardini, Natalia, Boomsma, Dorret I., Hottenga, Jouke J., Müller-Nurasyid, Martina, Ahluwalia, Tarunveer S., Stokholm, Jakob, Chawes, Bo, Schoos, Ann-Marie M., Esplugues, Ana, Bustamante, Mariona, Raby, Benjamin, Arshad, Syed, German, Chris, Esko, Tõnu, Milani, Lili A., Metspalu, Andres, Terao, Chikashi, Abuabara, Katrina, Løset, Mari, Hveem, Kristian, Jacobsson, Bo, Pino-Yanes, Maria, Strachan, David P., Grarup, Niels, Linneberg, Allan, Lee, Young-Ae, Probst-Hensch, Nicole, Weidinger, Stephan, Jarvelin, Marjo-Riitta, Melén, Erik, Hakonarson, Hakon, Irvine, Alan D., Jarvis, Deborah, Nijsten, Tamar, Duijts, Liesbeth, Vonk, Judith M., Koppelmann, Gerard H., Godfrey, Keith M., Barton, Sheila J., Feenstra, Bjarke, Pennell, Craig E., Sly, Peter D., Holt, Patrick G., Williams, L. Keoki, Bisgaard, Hans, Bønnelykke, Klaus, Curtin, John, Simpson, Angela, Murray, Clare, Schikowski, Tamara, Bunyavanich, Supinda, Weiss, Scott T., Holloway, John W., Min, Josine L., Brown, Sara J., Standl, Marie, and Paternoster, Lavinia

Published
2023
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7. Exploring Interaction between Genetically Predicted Body Mass Index and Serum 25-Hydroxyvitamin D Levels on the Odds for Psoriasis in UK Biobank and the HUNT Study: A Factorial Mendelian Randomization Study

Author

Jenssen, Marita, Arora, Nikhil, Løset, Mari, Åsvold, Bjørn Olav, Thomas, Laurent, Bekkevold Vassmyr, Ole-Jørgen, Mai, Xiao-Mei, Sun, Yi-Qian, Furberg, Anne-Sofie, Jorde, Rolf, Wilsgaard, Tom, Danielsen, Kjersti, and Brumpton, Ben Michael

Published
2024
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8. High-resolution regional sea-ice model based on the discrete element method with boundary conditions from a large-scale model for ice drift

Author

Andrei Tsarau, Wenjun Lu, Raed Lubbad, Sveinung Løset, and Yuan Zhang

Subjects
remote sensing, sea ice, sea-ice dynamics, sea-ice modelling, Meteorology. Climatology, QC851-999
Abstract

Understanding sea-ice dynamics at the floe scale is crucial to comprehend polar climate systems. While continuum models are commonly used to simulate large-scale sea-ice dynamics, they have limitations in accurately representing sea-ice behaviour at small scales. DEMs, on the other hand, are well-suited for modelling the behaviour of individual ice floes but face limitations due to computational constraints. To address the limitations of both approaches while combining their strengths, we explored the feasibility of using a DEM within a continuum model, where the latter provides boundary conditions for a rectangular high-resolution DEM domain. This paper presents a feasibility study where a discrete model of a 100 × 100 km2 icefield was created using high-resolution optical satellite imagery. Sea-ice dynamics were simulated in the DEM considering environmental forces and integrating large-scale ice-drift velocities as boundary conditions. Model predictions were compared with satellite observations for ice drift and deformation parameters. This numerical approach showed potential for offering accurate, high-resolution predictions of sea ice, particularly in coastal areas and near islands, and may find applications in ice navigation and climate studies. However, further development of the DEM, along with upgrades to the coupled ocean models providing data for the ice component, may be necessary. Additionally, challenges remain to develop a two-way coupling between the DEM and a continuum model, which may be needed to improve the accuracy of large-scale simulations.

Published
2024
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9. Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.

Author

Nielsen, Jonas B, Rom, Oren, Surakka, Ida, Graham, Sarah E, Zhou, Wei, Roychowdhury, Tanmoy, Fritsche, Lars G, Gagliano Taliun, Sarah A, Sidore, Carlo, Liu, Yuhao, Gabrielsen, Maiken E, Skogholt, Anne Heidi, Wolford, Brooke, Overton, William, Zhao, Ying, Chen, Jin, Zhang, He, Hornsby, Whitney E, Acheampong, Akua, Grooms, Austen, Schaefer, Amanda, Zajac, Gregory JM, Villacorta, Luis, Zhang, Jifeng, Brumpton, Ben, Løset, Mari, Rai, Vivek, Lundegaard, Pia R, Olesen, Morten S, Taylor, Kent D, Palmer, Nicholette D, Chen, Yii-Der, Choi, Seung H, Lubitz, Steven A, Ellinor, Patrick T, Barnes, Kathleen C, Daya, Michelle, Rafaels, Nicholas, Weiss, Scott T, Lasky-Su, Jessica, Tracy, Russell P, Vasan, Ramachandran S, Cupples, L Adrienne, Mathias, Rasika A, Yanek, Lisa R, Becker, Lewis C, Peyser, Patricia A, Bielak, Lawrence F, Smith, Jennifer A, Aslibekyan, Stella, Hidalgo, Bertha A, Arnett, Donna K, Irvin, Marguerite R, Wilson, James G, Musani, Solomon K, Correa, Adolfo, Rich, Stephen S, Guo, Xiuqing, Rotter, Jerome I, Konkle, Barbara A, Johnsen, Jill M, Ashley-Koch, Allison E, Telen, Marilyn J, Sheehan, Vivien A, Blangero, John, Curran, Joanne E, Peralta, Juan M, Montgomery, Courtney, Sheu, Wayne H-H, Chung, Ren-Hua, Schwander, Karen, Nouraie, Seyed M, Gordeuk, Victor R, Zhang, Yingze, Kooperberg, Charles, Reiner, Alexander P, Jackson, Rebecca D, Bleecker, Eugene R, Meyers, Deborah A, Li, Xingnan, Das, Sayantan, Yu, Ketian, LeFaive, Jonathon, Smith, Albert, Blackwell, Tom, Taliun, Daniel, Zollner, Sebastian, Forer, Lukas, Schoenherr, Sebastian, Fuchsberger, Christian, Pandit, Anita, Zawistowski, Matthew, Kheterpal, Sachin, Brummett, Chad M, Natarajan, Pradeep, Schlessinger, David, Lee, Seunggeun, Kang, Hyun Min, Cucca, Francesco, and Holmen, Oddgeir L

Subjects
Liver, Humans, Cardiovascular Diseases, Lipids, Receptors, LDL, Gene Targeting, Gene Silencing, Genome, Human, Biological Specimen Banks, Genome-Wide Association Study, Molecular Targeted Therapy, United Kingdom, Loss of Function Mutation, Phenomics
Abstract

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD.

Published
2020

10. Age-of-onset information helps identify 76 genetic variants associated with allergic disease.

Author

Ferreira, Manuel AR, Vonk, Judith M, Baurecht, Hansjörg, Marenholz, Ingo, Tian, Chao, Hoffman, Joshua D, Helmer, Quinta, Tillander, Annika, Ullemar, Vilhelmina, Lu, Yi, Grosche, Sarah, Rüschendorf, Franz, Granell, Raquel, Brumpton, Ben M, Fritsche, Lars G, Bhatta, Laxmi, Gabrielsen, Maiken E, Nielsen, Jonas B, Zhou, Wei, Hveem, Kristian, Langhammer, Arnulf, Holmen, Oddgeir L, Løset, Mari, Abecasis, Gonçalo R, Willer, Cristen J, Emami, Nima C, Cavazos, Taylor B, Witte, John S, Szwajda, Agnieszka, 23andMe Research Team, collaborators of the SHARE study, Hinds, David A, Hübner, Norbert, Weidinger, Stephan, Magnusson, Patrik Ke, Jorgenson, Eric, Karlsson, Robert, Paternoster, Lavinia, Boomsma, Dorret I, Almqvist, Catarina, Lee, Young-Ae, and Koppelman, Gerard H

Subjects
23andMe Research Team, collaborators of the SHARE study, Humans, Asthma, Eczema, Age of Onset, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Middle Aged, Child, Female, Rhinitis, Allergic, Seasonal, Male, Genome-Wide Association Study, Genetic Loci, Polymorphism, Single Nucleotide, Rhinitis, Allergic, Seasonal, Developmental Biology, Genetics
Abstract

Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P

Published
2020

16. The HUNT study: A population-based cohort for genetic research

Author

Brumpton, Ben M., Graham, Sarah, Surakka, Ida, Skogholt, Anne Heidi, Løset, Mari, Fritsche, Lars G., Wolford, Brooke, Zhou, Wei, Nielsen, Jonas Bille, Holmen, Oddgeir L., Gabrielsen, Maiken E., Thomas, Laurent, Bhatta, Laxmi, Rasheed, Humaira, Zhang, He, Kang, Hyun Min, Hornsby, Whitney, Moksnes, Marta Riise, Coward, Eivind, Melbye, Mads, Giskeødegård, Guro F., Fenstad, Jørn, Krokstad, Steinar, Næss, Marit, Langhammer, Arnulf, Boehnke, Michael, Abecasis, Gonçalo R., Åsvold, Bjørn Olav, Hveem, Kristian, and Willer, Cristen J.

Published
2022
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20. B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells

Author

Annabel R. Minton, Lindsay D. Smith, Dean J. Bryant, Jonathan C. Strefford, Francesco Forconi, Freda K. Stevenson, Edd James, Geir Åge Løset, Ludvig A. Munthe, Andrew J. Steele, and Graham Packham

Subjects
chronic lymphocytic leukemia, antigen presentation, t helper cell, b-cell receptor, phagocytosis, major histocompatibility complex class ii, human leukocyte antigen class ii, Internal medicine, RC31-1245
Abstract

Aim: T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL cells can present soluble antigens targeted from the B-cell receptor to T-helper cells via major histocompatibility complex (MHC) class II, antigens recognized by some CLL cells may be encountered in a particulate form. Here the ability of CLL cells to internalize and present anti-immunoglobulin M (IgM) beads as a model for the interaction of CLL cells with particulate antigens was investigated. Methods: The effect of anti-IgM beads on antigen presentation pathways was analyzed using RNA-seq and internalization of anti-IgM beads by primary CLL cells was investigated using confocal microscopy and flow cytometry. Antigen presentation was investigated by analyzing activation of a T-cell line expressing a T-cell receptor specific for a peptide derived from mouse κ light chains after incubating CLL cells with a mouse κ light chain-containing anti-IgM monoclonal antibody. Kinase inhibitors were used to characterize the pathways mediating internalization and antigen presentation. Results: Stimulation of surface IgM of CLL cells increased expression of the antigen presentation machinery and CLL cells were able to phagocytose anti-IgM beads. Internalization of anti-IgM beads was associated with MHC class II-restricted activation of cognate T-helper cells. Antigen presentation by CLL cells was dependent on activity of spleen tyrosine kinase (SYK) and phosphatidylinositol 3-kinase delta (PI3Kδ) but was unaffected by inhibitors of Bruton’s tyrosine kinase (BTK). Conclusions: CLL cells can internalize and present antigen from anti-IgM beads. This capacity of CLL cells may be particularly important for recruitment of T-cell help in vivo in response to particulate antigens.

Published
2022
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21. Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

Author

Brittany L. Mitchell, Jake R. Saklatvala, Nick Dand, Fiona A. Hagenbeek, Xin Li, Josine L. Min, Laurent Thomas, Meike Bartels, Jouke Jan Hottenga, Michelle K. Lupton, Dorret I. Boomsma, Xianjun Dong, Kristian Hveem, Mari Løset, Nicholas G. Martin, Jonathan N. Barker, Jiali Han, Catherine H. Smith, Miguel E. Rentería, and Michael A. Simpson

Subjects
Science
Abstract

Better understanding of the genetic basis of acne can pave the way to more effective treatments. Here, the authors perform a genome-wide association study meta-analysis of >20,000 cases and identify 29 new acne susceptibility loci, uncovering genetic links to Mendelian hair and skin disorders and other complex traits.

Published
2022
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22. Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

Author

Mitchell, Brittany L., Saklatvala, Jake R., Dand, Nick, Hagenbeek, Fiona A., Li, Xin, Min, Josine L., Thomas, Laurent, Bartels, Meike, Jan Hottenga, Jouke, Lupton, Michelle K., Boomsma, Dorret I., Dong, Xianjun, Hveem, Kristian, Løset, Mari, Martin, Nicholas G., Barker, Jonathan N., Han, Jiali, Smith, Catherine H., Rentería, Miguel E., and Simpson, Michael A.

Published
2022
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23. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

Author

Ferreira, Manuel A, Vonk, Judith M, Baurecht, Hansjörg, Marenholz, Ingo, Tian, Chao, Hoffman, Joshua D, Helmer, Quinta, Tillander, Annika, Ullemar, Vilhelmina, van Dongen, Jenny, Lu, Yi, Rüschendorf, Franz, Esparza-Gordillo, Jorge, Medway, Chris W, Mountjoy, Edward, Burrows, Kimberley, Hummel, Oliver, Grosche, Sarah, Brumpton, Ben M, Witte, John S, Hottenga, Jouke-Jan, Willemsen, Gonneke, Zheng, Jie, Rodríguez, Elke, Hotze, Melanie, Franke, Andre, Revez, Joana A, Beesley, Jonathan, Matheson, Melanie C, Dharmage, Shyamali C, Bain, Lisa M, Fritsche, Lars G, Gabrielsen, Maiken E, Balliu, Brunilda, Nielsen, Jonas B, Zhou, Wei, Hveem, Kristian, Langhammer, Arnulf, Holmen, Oddgeir L, Løset, Mari, Abecasis, Gonçalo R, Willer, Cristen J, Arnold, Andreas, Homuth, Georg, Schmidt, Carsten O, Thompson, Philip J, Martin, Nicholas G, Duffy, David L, Novak, Natalija, Schulz, Holger, Karrasch, Stefan, Gieger, Christian, Strauch, Konstantin, Melles, Ronald B, Hinds, David A, Hübner, Norbert, Weidinger, Stephan, Magnusson, Patrik KE, Jansen, Rick, Jorgenson, Eric, Lee, Young-Ae, Boomsma, Dorret I, Almqvist, Catarina, Karlsson, Robert, Koppelman, Gerard H, and Paternoster, Lavinia

Subjects
Biological Sciences, Genetics, Clinical Research, Human Genome, Lung, Asthma, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Eczema, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypersensitivity, Phenotype, Polymorphism, Single Nucleotide, Rhinitis, Allergic, Seasonal, Risk Factors, 23andMe Research Team, AAGC collaborators, BIOS consortium, LifeLines Cohort Study, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Published
2017

34. Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease

Author

Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Nicholette D. Palmer, Yii-Der Chen, Seung H. Choi, Steven A. Lubitz, Patrick T. Ellinor, Kathleen C. Barnes, Michelle Daya, Nicholas Rafaels, Scott T. Weiss, Jessica Lasky-Su, Russell P. Tracy, Ramachandran S. Vasan, L. Adrienne Cupples, Rasika A. Mathias, Lisa R. Yanek, Lewis C. Becker, Patricia A. Peyser, Lawrence F. Bielak, Jennifer A. Smith, Stella Aslibekyan, Bertha A. Hidalgo, Donna K. Arnett, Marguerite R. Irvin, James G. Wilson, Solomon K. Musani, Adolfo Correa, Stephen S. Rich, Xiuqing Guo, Jerome I. Rotter, Barbara A. Konkle, Jill M. Johnsen, Allison E. Ashley-Koch, Marilyn J. Telen, Vivien A. Sheehan, John Blangero, Joanne E. Curran, Juan M. Peralta, Courtney Montgomery, Wayne H-H Sheu, Ren-Hua Chung, Karen Schwander, Seyed M. Nouraie, Victor R. Gordeuk, Yingze Zhang, Charles Kooperberg, Alexander P. Reiner, Rebecca D. Jackson, Eugene R. Bleecker, Deborah A. Meyers, Xingnan Li, Sayantan Das, Ketian Yu, Jonathon LeFaive, Albert Smith, Tom Blackwell, Daniel Taliun, Sebastian Zollner, Lukas Forer, Sebastian Schoenherr, Christian Fuchsberger, Anita Pandit, Matthew Zawistowski, Sachin Kheterpal, Chad M. Brummett, Pradeep Natarajan, David Schlessinger, Seunggeun Lee, Hyun Min Kang, Francesco Cucca, Oddgeir L. Holmen, Bjørn O. Åsvold, Michael Boehnke, Sekar Kathiresan, Goncalo R. Abecasis, Y. Eugene Chen, Cristen J. Willer, and Kristian Hveem

Subjects
Science
Abstract

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

Published
2020
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39. Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease

Author

Høydahl, Lene Støkken, Richter, Lisa, Frick, Rahel, Snir, Omri, Gunnarsen, Kristin Støen, Landsverk, Ole J.B., Iversen, Rasmus, Jeliazkov, Jeliazko R., Gray, Jeffrey J., Bergseng, Elin, Foss, Stian, Qiao, Shuo-Wang, Lundin, Knut E.A., Jahnsen, Jørgen, Jahnsen, Frode L., Sandlie, Inger, Sollid, Ludvig M., and Løset, Geir Åge

Published
2019
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40. Socioeconomic Inequalities in Mortality After Age 67: The Contribution of Psychological Factors

Author

Marijke Veenstra, Gøril Kvamme Løset, and Svein Olav Daatland

Subjects
life span developmental theory, aging, socioeconomic inequalities, mortality, perceived control, subjective age, Psychology, BF1-990
Abstract

Diverging trends of longer lives and increased inequalities in age-at-death invite to updated research on late-life mortality. Earlier studies have identified health behavior, childhood, psychosocial, and material conditions as key determinants of life expectancy, but the role of psychological factors remains a topic of debate. The current study is framed in a life course developmental perspective and assesses the mediating role of secondary control strategies (subjective age) and primary control capacity (perceived control) to socioeconomic (wealth and education) inequality in mortality after age 67. Data are derived from the second wave of the Norwegian Life Course, Ageing and Generation study (N=1,432 and age 67–85). All in all, 366 deaths were observed over a mean follow-up of 9.6years. Perceived control was measured by the Pearlin and Schooler Mastery Scale. SA was measured with proportional discrepancy scores in felt age and ideal age. Stepwise Cox proportional hazards regression analyses were conducted to analyze the relative contribution of SES (education and accumulated wealth), felt age, and ideal age discrepancies and perceived control on 11-year mortality. Findings show that lower levels of wealth and perceived control independently predict increased elderly mortality over an 11-year period. Feeling younger and smaller ideal age discrepancies are positively associated with perceived control, but do not account for additional variability in longevity among older adults. Findings add to the interdisciplinary field of socioeconomic inequalities in elderly mortality and underline the specific importance of structural conditions (wealth) and the continued importance of (perceived) primary control capacity for longevity also after age 67. Future research may assess in more detail how wealth and perceived control complement each other in contributing to healthy aging and longevity, for example, by longitudinal research including the role of significant life events in the second half of life in different welfare state contexts.

Published
2021
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48. Age-of-onset information helps identify 76 genetic variants associated with allergic disease.

Author

Manuel A R Ferreira, Judith M Vonk, Hansjörg Baurecht, Ingo Marenholz, Chao Tian, Joshua D Hoffman, Quinta Helmer, Annika Tillander, Vilhelmina Ullemar, Yi Lu, Sarah Grosche, Franz Rüschendorf, Raquel Granell, Ben M Brumpton, Lars G Fritsche, Laxmi Bhatta, Maiken E Gabrielsen, Jonas B Nielsen, Wei Zhou, Kristian Hveem, Arnulf Langhammer, Oddgeir L Holmen, Mari Løset, Gonçalo R Abecasis, Cristen J Willer, Nima C Emami, Taylor B Cavazos, John S Witte, Agnieszka Szwajda, andMe Research Team, collaborators of the SHARE study, David A Hinds, Norbert Hübner, Stephan Weidinger, Patrik Ke Magnusson, Eric Jorgenson, Robert Karlsson, Lavinia Paternoster, Dorret I Boomsma, Catarina Almqvist, Young-Ae Lee, and Gerard H Koppelman

Subjects
Genetics, QH426-470
Abstract

Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P

Published
2020
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49. A large scale simulation of floe-ice fractures and validation against full-scale scenario

Author

Wenjun Lu, Hans-Martin Heyn, Raed Lubbad, and Sveinung Løset

Subjects
Ocean engineering, TC1501-1800, Naval architecture. Shipbuilding. Marine engineering, VM1-989
Abstract

While interacting with a sloping structure, an ice floe may fracture in different patterns. For example, it can be local bending failure or global splitting failure depending on the contact properties, geometry and confinement of the ice floe. Modelling these different fracture patterns as a natural outcome of numerical simulations is rather challenging. This is mainly because the effects of crack propagation, crack branching, multi fracturing modes and eventual fragmentation within a solid material are still questions to be answered by the on-going research in the Computational Mechanic community. In order to simulate the fracturing of ice floes with arbitrary geometries and confinement; and also to simulate the fracturing events at such a large scale yet with sufficient efficiency, we propose a semi-analytical/empirical and semi-numerical approach; but with focus on the global splitting failure mode in this paper. The simulation method is validated against data we collected during the Oden Arctic Technology Research Cruise 2015 (OATRC2015). The data include: 1) camera images based on which we specify the exact geometry of ice floes before and after an impact and fracturing event; 2) IMU data based on which the global dynamic force encountered by the icebreaker is extracted for the impact event. It was found that this method presents reasonably accurate results and realistic fracturing patterns upon given ice floes. Keywords: Icebreaker, Ice, Splitting, XFEM, IMU

Published
2018
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50. Genome-wide meta-analysis implicates variation affecting mast cell biology in urticaria

Author

McSweeney, Sheila Mary, primary, Saklatvala, Jake, additional, Rispoli, Rossella, additional, Ganier, Clarisse, additional, Woszczek, Grzegorz, additional, Thomas, Laurent, additional, Hveem, Kristian, additional, Løset, Mari, additional, Dand, Nick, additional, Tziotzios, Christos, additional, Simpson, Michael, additional, and McGrath, John Alexander, additional

Published
2023
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