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Sökning: onr:"swepub:oai:DiVA.org:uu-450774" > A novel whole blood...

A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents

Lemonnier, Nathanaël (författare)
UGA, INSERM U1209, CNRS, UMR5309,Inst Adv Biosci, Site Sante,Allee Alpes, F-38700 La Tronche, France.
Melen, Erik (författare)
Karolinska Institutet
Jiang, Yale (författare)
Univ Pittsburgh, UPMC Childrens Hosp Pittsburgh, Div Pediat Pulm Med, Pittsburgh, PA USA.;Tsinghua Univ, Sch Med, Beijing, Peoples R China.
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Joly, Stephane (författare)
INSERM, Int Ctr Infectiol Res, CIRI, Lyon, France.
Menard, Camille (författare)
INSERM, Int Ctr Infectiol Res, CIRI, Lyon, France.
Aguilar, Daniel (författare)
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Barcelona, Spain.
Acosta-Perez, Edna (författare)
Univ Puerto Rico, Behav Sci Res Inst, San Juan, PR 00936 USA.
Bergstrom, Anna (författare)
Karolinska Institutet
Boutaoui, Nadia (författare)
Univ Pittsburgh, UPMC Childrens Hosp Pittsburgh, Div Pediat Pulm Med, Pittsburgh, PA USA.
Bustamante, Mariona (författare)
Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.;UPF, Barcelona, Spain.;Inst Salud Carlos III, Spanish Consortium Res Epidemiol & Publ Hlth CIBE, Madrid, Spain.
Canino, Glorisa (författare)
Univ Puerto Rico, Behav Sci Res Inst, San Juan, PR 00936 USA.
Forno, Erick (författare)
Univ Pittsburgh, UPMC Childrens Hosp Pittsburgh, Div Pediat Pulm Med, Pittsburgh, PA USA.
Ramon Gonzalez, Juan (författare)
Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.
Garcia-Aymerich, Judith (författare)
Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.
Gruzieva, Olena (författare)
Karolinska Institutet
Guerra, Stefano (författare)
Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.;Univ Arizona, Asthma & Airway Dis Res Ctr, Tucson, AZ USA.
Heinrich, Joachim (författare)
Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Munich, Germany.;Univ Hosp Munich LMU, Inner City Clin, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany.
Kull, Inger (författare)
Karolinska Institutet
Ibarluzea Maurolagoitia, Jesus (författare)
Inst Salud Carlos III, Spanish Consortium Res Epidemiol & Publ Hlth CIBE, Madrid, Spain.;BIODONOSTIA, Inst Invest Sanitaria, Donostia San Sebastian, Spain.
Santa-Marina Rodriguez, Loreto (författare)
Inst Salud Carlos III, Spanish Consortium Res Epidemiol & Publ Hlth CIBE, Madrid, Spain.
Thiering, Elisabeth (författare)
Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Munich, Germany.;Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutr Med, Munich, Germany.
Wickman, Magnus (författare)
Uppsala universitet,Centrum för klinisk forskning i Sörmland (CKFD)
Akdis, Cezmi (författare)
Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland.
Akdis, Mübeccel (författare)
Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland.
Chen, Wei (författare)
Univ Pittsburgh, UPMC Childrens Hosp Pittsburgh, Div Pediat Pulm Med, Pittsburgh, PA USA.;Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
Keil, Thomas (författare)
Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany.;Univ Wurzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany.;Bavarian Hlth & Food Safety Author, Inst Hlth Resort Med & Hlth Promot, Bad Kissingen, Germany.
Koppelman, Gerard H. (författare)
Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands.
Siroux, Valerie (författare)
UGA, INSERM U1209, CNRS, UMR5309,Inst Adv Biosci, Site Sante,Allee Alpes, F-38700 La Tronche, France.
Xu, Cheng-Jian (författare)
Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands.
Hainaut, Pierre (författare)
UGA, INSERM U1209, CNRS, UMR5309,Inst Adv Biosci, Site Sante,Allee Alpes, F-38700 La Tronche, France.
Standl, Marie (författare)
Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Munich, Germany.
Sunyer, Jordi (författare)
Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.
Celedon, Juan C. (författare)
Univ Pittsburgh, UPMC Childrens Hosp Pittsburgh, Div Pediat Pulm Med, Pittsburgh, PA USA.
Maria Anto, Josep (författare)
Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.
Bousquet, Jean (författare)
Fdn Partenariale FMC VIA LR, MACVIA France, Montpellier, France.;Univ Versailles St Quentin En Yvelines, UMR S 1168, Ageing & Chron Dis Epidemiol & Publ Hlth Approach, Montigny Le Bretonneux, France.;Euforea, Brussels, Belgium.;Charite, Comprehens Allergy Ctr, Dept Dermatol & Allergy, Berlin, Germany.
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Karolinska Institutet UGA, INSERM U1209, CNRS, UMR5309,Inst Adv Biosci, Site Sante,Allee Alpes, F-38700 La Tronche, France (creator_code:org_t)
2020-04-23
2020
Engelska.
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

asthma
atopic dermatitis
multimorbidity
rhinitis
transcriptomics

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