المؤلفون: Stölzl, D., Sander, N., Siegels, D., Harder, I., Kind, B., Fonfara, M., Heinrich, L., Ott, Hagen, Abraham, S., Neustädter, I., Kleinheinz, A., Gerdes, S., Wollenberg, A., Lau, S., Nemat, K., Heratizadeh, A., Gellhaus, I., Werfel, T., Schmitt, J., Weidinger, S.

المصدر: Allergy ; ISSN 0105-4538 1398-9995

الإتاحة: https://doi.org/10.1111/all.16147Test

المؤلفون: Stölzl, D., Sander, N., Heratizadeh, A., Haufe, E., Harder, I., Abraham, S., Heinrich, L., Kleinheinz, A., Wollenberg, A., Weisshaar, E., Schäkel, K., Ertner, K., Wiemers, F., Wildberger, J., Worm, M., von Kiedrowski, R., Effendy, I., Asmussen, A., Augustin, M., Pawlak, M., Sticherling, M., Zink, A., Hilgers, M., Handrick, C., Quist, S., Schwarz, B., Staubach-Renz, P., Bell, M., Hong-Weldemann, S.H., Homey, B., Brücher, J.J., Schmitt, J., Werfel, T., Weidinger, S.

المصدر: Br. J. Dermatol., DOI:10.1111/bjd.21794 (2022)

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35895855; info:eu-repo/semantics/altIdentifier/isbn/0007-0963; info:eu-repo/semantics/altIdentifier/pissn/0007-0963; info:eu-repo/semantics/altIdentifier/ei; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=66034Test; urn:isbn:0007-0963; urn:issn:0007-0963; urn:issn:1365-2133

الإتاحة: https://doi.org/10.1111/bjd.21794Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=66034Test

المؤلفون: Sander, N., Stölzl, D., Heratizdaeh, A., Haufe, E., Harder, I., Schmitt, J., Werfel, T., Weidinger, S.

المصدر: Journal of Investigative Dermatology ; volume 142, issue 12, page S196 ; ISSN 0022-202X

مصطلحات موضوعية: Cell Biology, Dermatology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1016/j.jid.2022.09.102Test
https://api.elsevier.com/content/article/PII:S0022202X2202036X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0022202X2202036X?httpAccept=text/plainTest

المؤلفون: Fonfara, M., Hartmann, J., Sander, N., Harder, I., Stölzl, D., Rodriguez, E., Kabesch, M., Schmitt, J., Weidinger, S., Emmert, H.

المصدر: Journal of Investigative Dermatology ; volume 142, issue 12, page S247 ; ISSN 0022-202X

مصطلحات موضوعية: Cell Biology, Dermatology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1016/j.jid.2022.09.403Test
https://api.elsevier.com/content/article/PII:S0022202X22023375?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0022202X22023375?httpAccept=text/plainTest

المؤلفون: Grosche, S. (Sarah), Marenholz, I. (Ingo), Esparza-Gordillo, J. (Jorge), Arnau-Soler, A. (Aleix), Pairo-Castineira, E. (Erola), Rueschendorf, F. (Franz), Ahluwalia, T. S. (Tarunveer S.), Almqvist, C. (Catarina), Arnold, A. (Andreas), Baurecht, H. (Hansjoerg), Bisgaard, H. (Hans), Bonnelykke, K. (Klaus), Brown, S. J. (Sara J.), Bustamante, M. (Mariona), Curtin, J. A. (John A.), Custovic, A. (Adnan), Dharmage, S. C. (Shyamali C.), Esplugues, A. (Ana), Falchi, M. (Mario), Fernandez-Orth, D. (Dietmar), Ferreira, M. A. (Manuel A. R.), Franke, A. (Andre), Gerdes, S. (Sascha), Gieger, C. (Christian), Hakonarson, H. (Hakon), Holt, P. G. (Patrick G.), Homuth, G. (Georg), Hubner, N. (Norbert), Hysi, P. G. (Pirro G.), Järvelin, M.-R. (Marjo-Riitta), Karlsson, R. (Robert), Koppelman, G. H. (Gerard H.), Lau, S. (Susanne), Lutz, M. (Manuel), Magnusson, P. K. (Patrik K. E.), Marks, G. B. (Guy B.), Mueller-Nurasyid, M. (Martina), Noethen, M. M. (Markus M.), Paternoster, L. (Lavinia), Pennell, C. E. (Craig E.), Peters, A. (Annette), Rawlik, K. (Konrad), Robertson, C. F. (Colin F.), Rodriguez, E. (Elke), Sebert, S. (Sylvain), Simpson, A. (Angela), Sleiman, P. M. (Patrick M. A.), Standl, M. (Marie), Stoelzl, D. (Dora), Strauch, K. (Konstantin), Szwajda, A. (Agnieszka), Tenesa, A. (Albert), Thompson, P. J. (Philip J.), Ullemar, V. (Vilhelmina), Visconti, A. (Alessia), Vonk, J. M. (Judith M.), Wang, C. A. (Carol A.), Weidinger, S. (Stephan), Wielscher, M. (Matthias), Worth, C. L. (Catherine L.), Xu, C.-J. (Chen-Jian), Lee, Y.-A. (Young-Ae)

الوصف: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

وصف الملف: application/pdf

الإتاحة: http://urn.fi/urn:nbn:fi-fe2022040527097Test

المؤلفون: Grosche, S, Marenholz, I, Esparza-Gordillo, J, Arnau-Soler, A, Pairo-Castineira, E, Rueschendorf, F, Ahluwalia, TS, Almqvist, C, Arnold, A, Baurecht, H, Bisgaard, H, Bonnelykke, K, Brown, SJ, Bustamante, M, Curtin, JA, Custovic, A, Dharmage, SC, Esplugues, A, Falchi, M, Fernandez-Orth, D, Ferreira, MAR, Franke, A, Gerdes, S, Gieger, C, Hakonarson, H, Holt, PG, Homuth, G, Hubner, N, Hysi, PG, Jarvelin, M-R, Karlsson, R, Koppelman, GH, Lau, S, Lutz, M, Magnusson, PKE, Marks, GB, Mueller-Nurasyid, M, Noethen, MM, Paternoster, L, Pennell, CE, Peters, A, Rawlik, K, Robertson, CF, Rodriguez, E, Sebert, S, Simpson, A, Sleiman, PMA, Standl, M, Stoelzl, D, Strauch, K, Szwajda, A, Tenesa, A, Thompson, PJ, Ullemar, V, Visconti, A, Vonk, JM, Wang, CA, Weidinger, S, Wielscher, M, Worth, CL, Xu, C-J, Lee, Y-A

الوصف: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

العلاقة: pii: 10.1038/s41467-021-26783-x; Grosche, S., Marenholz, I., Esparza-Gordillo, J., Arnau-Soler, A., Pairo-Castineira, E., Rueschendorf, F., Ahluwalia, T. S., Almqvist, C., Arnold, A., Baurecht, H., Bisgaard, H., Bonnelykke, K., Brown, S. J., Bustamante, M., Curtin, J. A., Custovic, A., Dharmage, S. C., Esplugues, A., Falchi, M. ,. Lee, Y. -A. (2021). Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4. NATURE COMMUNICATIONS, 12 (1), https://doi.org/10.1038/s41467-021-26783-xTest.; http://hdl.handle.net/11343/296384Test

الإتاحة: https://doi.org/10.1038/s41467-021-26783-xTest
http://hdl.handle.net/11343/296384Test

المؤلفون: Grosche, S., Marenholz, I., Esparza-Gordillo, J., Arnau-Soler, A., Pairo-Castineira, E., Rüschendorf, F., Ahluwalia, T.S., Almqvist, C., Arnold, A., Baurecht, H., Bisgaard, H., Bønnelykke, K., Brown, S.J., Bustamante, M., Curtin, J.A., Custovic, A., Dharmage, S.C., Esplugues, A., Falchi, M., Fernandez-Orth, D., Ferreira, M.A.R., Franke, A., Gerdes, S., Gieger, C., Hakonarson, H., Holt, P.G., Homuth, G., Hubner, N., Hysi, P.G., Jarvelin, M.R., Karlsson, R., Koppelman, G.H., Lau, S., Lutz, M., Magnusson, P.K.E., Marks, G.B., Müller-Nurasyid, M., Nöthen, M.M., Paternoster, L., Pennell, C.E., Peters, A., Rawlik, K., Robertson, C.F., Rodriguez, E., Sebert, S., Simpson, A., Sleiman, P.M.A., Standl, M., Stölzl, D., Strauch, K., Szwajda, A., Tenesa, A., Thompson, P.J., Ullemar, V., Visconti, A., Vonk, J.M., Wang, C.A., Weidinger, S., Wielscher, M., Sargent, C.L., Xu, C.J., Lee, Y.A.

مصطلحات موضوعية: Cardiovascular and Metabolic Diseases, Topic 1: Genes, Cells and Cell-Based Medicine, Topic 3: Integrative Biomedicine

الوصف: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

وصف الملف: application/pdf; other

العلاقة: http://edoc.mdc-berlin.de/21087/1/21087oa.pdfTest; http://edoc.mdc-berlin.de/21087/4/21087suppl.zipTest; Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4. Grosche, S. and Marenholz, I. and Esparza-Gordillo, J. and Arnau-Soler, A. and Pairo-Castineira, E. and Rüschendorf, F. and Ahluwalia, T.S. and Almqvist, C. and Arnold, A. and Baurecht, H. and Bisgaard, H. and Bønnelykke, K. and Brown, S.J. and Bustamante, M. and Curtin, J.A. and Custovic, A. and Dharmage, S.C. and Esplugues, A. and Falchi, M. and Fernandez-Orth, D. and Ferreira, M.A.R. and Franke, A. and Gerdes, S. and Gieger, C. and Hakonarson, H. and Holt, P.G. and Homuth, G. and Hubner, N. and Hysi, P.G. and Jarvelin, M.R. and Karlsson, R. and Koppelman, G.H. and Lau, S. and Lutz, M. and Magnusson, P.K.E. and Marks, G.B. and Müller-Nurasyid, M. and Nöthen, M.M. and Paternoster, L. and Pennell, C.E. and Peters, A. and Rawlik, K. and Robertson, C.F. and Rodriguez, E. and Sebert, S. and Simpson, A. and Sleiman, P.M.A. and Standl, M. and Stölzl, D. and Strauch, K. and Szwajda, A. and Tenesa, A. and Thompson, P.J. and Ullemar, V. and Visconti, A. and Vonk, J.M. and Wang, C.A. and Weidinger, S. and Wielscher, M. and Sargent, C.L. and Xu, C.J. and Lee, Y.A. Nature Communications 12 (1): 6618. 16 November 2021

الإتاحة: https://doi.org/10.1038/s41467-021-26783-xTest
http://edoc.mdc-berlin.de/21087Test/
https://edoc.mdc-berlin.de/21087Test/
http://edoc.mdc-berlin.de/21087/1/21087oa.pdfTest
http://edoc.mdc-berlin.de/21087/4/21087suppl.zipTest

المؤلفون: Heratizadeh, A., Haufe, E., Stölzl, D., Abraham, S., Heinrich, L., Kleinheinz, A., Wollenberg, A., Weisshaar, E., Augustin, M., Wiemers, F., Zink, A., von Kiedrowski, R., Hilgers, M., Worm, M., Pawlak, M., Sticherling, M., Fell, I., Handrick, C., Schäkel, K., Staubach‐Renz, P., Asmussen, A., Schwarz, B., Bell, M., Effendy, I., Bieber, T., Homey, B., Gerlach, B., Tchitcherina, E., Stahl, M., Schwichtenberg, U., Rossbacher, J., Buck, P., Mempel, M., Beissert, S., Biedermann, T., Weidinger, S., Schmitt, J., Werfel, T.

مصطلحات موضوعية: ddc:610

الوصف: Background The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the ‘real‐life’ situation of health care for patients with AD. Objectives Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. Methods Patients (≥18 years) with moderate‐to‐severe AD [objective (o)SCORAD > 20], or with current or previous anti‐inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0–72), the oSCORAD (0–83) and the Investigator Global Assessment (IGA; 6‐point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six‐step Likert scale]. Disease symptoms were assessed by the patient‐oriented eczema measure (POEM, 0–28) and numeric rating scales (NRS, 0–10). Health‐related quality of life was measured using the dermatological life quality index (DLQI, 0–30). Results A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either ‘current’ (12.1%) or ‘prescribed’ (31.4%) at baseline. Conclusions These ‘real‐life’ data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order ...

وصف الملف: application/pdf

العلاقة: https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/15850Test; urn:nbn:de:bvb:29-opus4-158509; https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-158509Test; https://doi.org/10.1111/jdv.16078Test; https://opus4.kobv.de/opus4-fau/files/15850/JDV_JDV16078.pdfTest

الإتاحة: https://doi.org/10.1111/jdv.16078Test
https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/15850Test
https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-158509Test
https://opus4.kobv.de/opus4-fau/files/15850/JDV_JDV16078.pdfTest

المؤلفون: Mucha, S., Baurecht, H., Novak, N., Rodríguez, E., Bej, S., Mayr, G., Emmert, H., Stölzl, D., Gerdes, S., Jung, E.S., Degenhardt, F., Hübenthal, M., Ellinghaus, E., Kässens, J.C., Wienbrandt, L., Lieb, W., Müller-Nurasyid, M., Hotze, M., Dand, N., Grosche, S., Marenholz, I., Arnold, A., Homuth, G., Schmidt, C.O., Wehkamp, U., Nöthen, M.M., Hoffmann, P., Paternoster, L., Standl, M., Bønnelykke, K., Ahluwalia, T.S., Bisgaard, H., Peters, A., Gieger, C., Waldenberger, M., Schulz, H., Strauch, K., Werfel, T., Lee, Y.A., Wolfien, M., Rosenstiel, P., Wolkenhauer, O., Schreiber, S., Franke, A., Weidinger, S., Ellinghaus, D.

المصدر: J. Allergy Clin. Immunol. 145, 1208-1218 (2020)

مصطلحات موضوعية: Atopic Dermatitis, Exome Chip Association Analysis, Network Analysis, Protein Sequence And Structural Domain Analysis, Rna Sequencing

الوصف: Background: Fifteen percent of atopic dermatitis (AD) liability-scale heritability could be attributed to 31 susceptibility loci identified by using genome-wide association studies, with only 3 of them (IL13, IL-6 receptor [IL6R], and filaggrin [FLG]) resolved to protein-coding variants.Objective: We examined whether a significant portion of unexplained AD heritability is further explained by low-frequency and rare variants in the gene-coding sequence.Methods: We evaluated common, low-frequency, and rare protein-coding variants using exome chip and replication genotype data of 15,574 patients and 377,839 control subjects combined with whole-transcriptome data on lesional, nonlesional, and healthy skin samples of 27 patients and 38 control subjects.Results: An additional 12.56% (SE, 0.74%) of AD heritability is explained by rare protein-coding variation. We identified docking protein 2 (DOK2) and CD200 receptor 1 (CD200R1) as novel genome-wide significant susceptibility genes. Rare coding variants associated with AD are further enriched in 5 genes (IL-4 receptor [IL4R], IL13, Janus kinase 1 [JAK1], JAK2, and tyrosine kinase 2 [TYK2]) of the IL13 pathway, all of which are targets for novel systemic AD therapeutics. Multiomics-based network and RNA sequencing analysis revealed DOK2 as a central hub interacting with, among others, CD200R1, IL6R, and signal transducer and activator of transcription 3 (STAT3). Multitissue gene expression profile analysis for 53 tissue types from the Genotype-Tissue Expression project showed that disease-associated protein-coding variants exert their greatest effect in skin tissues.Conclusion: Our discoveries highlight a major role of rare coding variants in AD acting independently of common variants. Further extensive functional studies are required to detect all potential causal variants and to specify the contribution of the novel susceptibility genes DOK2 and CD200R1 to overall disease susceptibility.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31707051; info:eu-repo/semantics/altIdentifier/wos/WOS:000523633400017; info:eu-repo/semantics/altIdentifier/isbn/0091-6749; info:eu-repo/semantics; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=57706Test; urn:isbn:0091-6749; urn:issn:0091-6749; urn:issn:1097-6825

الإتاحة: https://doi.org/10.1016/j.jaci.2019.10.030Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=57706Test

المؤلفون: Haufe, E, Stölzl, D, Heinrich, L, Abraham, S, Harder, I, Heratizadeh, A, Zink, A, Weisshaar, E, Bobylev, T, Kiedrowski, Rv, Worm, M, Baron, JM, Bell, M, Wollenberg, A, Neubert, K, Staubach-Renz, P, Bieber, T, Fell, I, Beissert, S, Werfel, T, Weidinger, S, Schmitt, J

المصدر: 17. Deutscher Kongress für Versorgungsforschung (DKVF); 20181010-20181012; Berlin; DOC18dkvf360 /20181012/

مصطلحات موضوعية: ddc: 610

العلاقة: http://dx.doi.org/10.3205/18dkvf360Test; http://nbn-resolving.de/urn:nbn:de:0183-18dkvf3601Test; http://www.egms.de/en/meetings/dkvf2018/18dkvf360.shtmlTest

الإتاحة: https://doi.org/10.3205/18dkvf360Test
http://nbn-resolving.de/urn:nbn:de:0183-18dkvf3601Test
http://www.egms.de/en/meetings/dkvf2018/18dkvf360.shtmlTest