GABRIEL - A multidisciplinary study to identify the genetic an environmental causes of asthma in the European community

Background
GABRIEL provides an integrated multidisciplinary program of post-genome research. Internationally leading groups will apply knowledge of epidemiology, genetics, genomics, proteomics, bioinformatics, statistics, environmental ecology and immunology into the causes of asthma in the European Community. Exceptional epidemiological and clinical surveys have already been assembled of childhood and adult asthma with inclusive information on environmental factors such as tobacco smoke, air pollution, nutrition, allergen exposure and industrial agents. This resource of 40.000 subjects will be extended to include severe asthmatics for genomic and proteomic analyses. GABRIEL will comprehensively screen candidate genes and perform whole-genome association studies to identify all important genetic influences on asthma with unmatched power to verify positive findings. The large body of results from the study will be exploited by statistical and bioinformatics groups experienced in handling data of this complexyty. GABRIEL will identify all important gene environment interactions underlying asthma in the European Community, and the results will be translated in cellular and genomic models to identify their molecular mechanisms. Farm study: Microbial exposures in rural farming environments result in a dramatic reduction in the development of asthma, indicating that effective tools for the prevention of asthma can be developed. The consortium will therefore systematically study rural farming environments. Cellular and genomic models to identify the molecular mechanisms of protective environments will be developed as screens for novel therapeutics and the commercialisation of the consortium results. Ethics: GABRIEL contains a strong and innovative ethical component, which will ensure integration of the results into the European knowledge base for patient understanding, disease prevention, and development of social policy.

Project Facts

Vonk J.M, Scholtens S, Postma D.S, Moffatt M.F, Jarvis D, Ramasamy A, Wjst M, Omenaas E.R, Bouzigon E, Demenais F, Nadif R, Siroux V, Polonikov A.V, Solodilova M, Ivanov V.P, Curjuric I, Imboden M, Kumar A, Probst-Hensch N, Ogorodova L.M, Puzyrev V.P, Bragina E.Y, Freidin M.B, Nolte I.M, Farrall A.M, Cookson W.O, Strachan D.P, Koppelman G.H, Boezen H.M. Adult onset asthma and interaction between genes and active tobacco smoking: the GABRIEL consortium. PLoS One. 2017;12(3):e0172716. DOI: 10.1371/journal.pone.0172716

Horak E, Morass B, Ulmer H, Genuneit J, Braun-Fahrländer C, von Mutius E. Prevalence of wheezing and atopic diseases in Austrian schoolchildren in conjunction with urban, rural or farm residence. Wien Klin Wochenschr. 2014;126(17-18):532-536. DOI: 10.1007/s00508-014-0571-z

Scholtens S, Postma D.S, Moffatt M.F, Panasevich S, Granell R, Henderson A.J, Melen E, Nyberg F, Pershagen G, Jarvis D, Ramasamy A, Wjst M, Svanes C, Bouzigon E, Demenais F, Kauffmann F, Siroux V, von Mutius E, Ege M.J, Braun-Fahrländer C, Genuneit J, Brunekreef B, Smit H.A, Wijga A.H, Kerkhof M, Curjuric I, Imboden M, Thun G.A, Probst-Hensch N, Freidin M.B, Bragina E.I, Deev I.A, Puzyrev V.P, Daley D, Park J, Becker A, Chan-Yeung M, Kozyrskyj A.L, Pare P, Marenholn I, Lau S, Keil T, Lee Y.A, Kabesch M, Wijmenga C, Franke L, Nolte I.M, Vonk J, Kumar A, Farrall M, Cookson W.O, Strachan D.P, Koppelman G.H, Boezen H.M. Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure [Letter to the editor]. J Allergy Clin Immunol. 2014;133(3):885-888. DOI: 10.1016/j.jaci.2013.08.049

Macneill S.J, Sozanska B, Danielewicz H, Debinska A, Kosmeda A, Boznanski A, Illi S, Depner M, Strunz-Lehner C, Waser M, Buchele G, Horak E, Genuneit J, Heederik D, Braun-Fahrländer C, von Mutius E, Cullinan P, GABRIELA Study Group. Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies. Allergy. 2013;68(6):771-779. DOI: 10.1111/all.12141

Bringolf-Isler B, Graf E, Waser M, Genuneit J, von Mutius E, Loss G, Kriemler S, Braun-Fahrländer C. Association of physical activity, asthma, and allergies: a cohort of farming and nonfarming children [Letter to the editor]. J Allergy Clin Immunol. 2013;132(3):743-746.e4. DOI: 10.1016/j.jaci.2013.03.042

Mélen E, Granell R, Kogevinas M, Strachan D, Gonzalez J.R, Wjst M, Jarvis D, Ege M, Braun-Fahrländer C, Genuneit J, Horak E, Bouzigon E, Demenais F, Kauffmann F, Siroux V, Michel S, von Berg A, Heinzmann A, Kabesch M, Probst-Hensch N.M, Curjuric I, Imboden M, Rochat T, Henderson J, Sterne J.A.C, McArdle W.L, Hui J, James A.L, Musk A.W, Palmer L.J, Becker A, Kozyrskyj A.L, Chan-Young M, Park J.E, Leung A, Daley D, Freidin M.B, Deev I.A, Ogorodova L.M, Puzyrev V.P, Celedón J.C, Brehm J.M, Cloutier M.M, Canino G, Acosta-Pérez E, Soto-Quiros M, Avila L, Bergström A, Magnusson J, Söderhäll C, Kull I, Scholtens S, Boezen H.M, Koppelman G.H, Wijga A.H, Marenholz I, Esparza-Gordillo J, Lau S, Lee Y.A, Standl M, Tiesler C.M.T, Flexeder C, Heinrich J, Myers R.A, Ober C, Nicolae D.L, Farrall M, Kumar A, Moffatt M.F, Cookson W.O.C.M, Lasky-Su J. Genome-wide association study of body mass index in 23,000 individuals with and without asthma. Clin Exp Allergy. 2013;43(4):463-474. DOI: 10.1111/cea.12054

Stöcklin L, Loss G, von Mutius E, Weber J, Genuneit J, Horak E, Sozanska B, Danielewicz H, Cullinan P, Heederik D, Braun-Fahrländer C, GABRIEL study group. Health-related quality of life in rural children living in four European countries: the GABRIEL study. Int J Public Health. 2013;58(3):355-366. DOI: 10.1007/s00038-012-0410-9

Genuneit J, Strachan D.P, Buchele G, Weber J, Loss G, Sozanska B, Boznanski A, Horak E, Heederik D, Braun-Fahrländer C, von Mutius E. The combined effects of family size and farm exposure on childhood hay fever and atopy. Pediatr Allergy Immunol. 2013;24(3):293-298. DOI: 10.1111/pai.12053

Stöcklin L, Loss G, von Mutius E, Genuneit J, Horak E, Braun-Fahrländer C, GABRIEL study group. Health-related quality of life does not explain the protective effect of farming on allergies. Pediatr Allergy Immunol. 2012;23(6):519-521. DOI: 10.1111/j.1399-3038.2012.01305.x

Fuchs O, Genuneit J, Latzin P, Buchele G, Horak E, Loss G, Sozanska B, Weber J, Boznanski A, Heederik D, Braun-Fahrländer C, Frey U, von Mutius E. Farming environments and childhood atopy, wheeze, lung function, and exhaled nitric oxide. J Allergy Clin Immunol. 2012;130(2):382-388.e6. DOI: 10.1016/j.jaci.2012.04.049

Illi S, Depner M, Genuneit J, Horak E, Loss G, Strunz-Lehner C, Buchele G, Boznanski A, Danielewicz H, Cullinan P, Heederik D, Braun-Fahrländer C, von Mutius E, GABRIELA Study Group. Protection from childhood asthma and allergy in Alpine farm environments - the GABRIEL Advanced Studies. J Allergy Clin Immunol. 2012;129(6):1470-1477. DOI: 10.1016/j.jaci.2012.03.013

Loss G, Apprich S, Kneifel W, von Mutius E, Genuneit J, Braun-Fahrländer C. Short communication: appropriate and alternative methods to determine viable bacterial counts in cow milk samples. J Dairy Sci. 2012;95(6):2916-2918. DOI: 10.3168/jds.2011-4897

Holbreich M, Genuneit J, Weber J, Braun-Fahrländer C, von Mutius E. The prevalence of asthma, hay fever and allergic sensitization in Amish children. J Allergy Clin Immunol, 2012;129(2 Suppl.):AB130

Normand A.C, Sudre B, Vacheyrou M, Depner M, Wouters I.M, Noss I, Heederik D, Hyvarinen A, Genuneit J, Braun-Fahrländer C, von Mutius E, Piarroux R, the GABRIEL-A Study Group. Airborne cultivable microflora and microbial transfer in farm buildings and rural dwellings. Occup Environ Med. 2011;68(11):849-855. DOI: 10.1136/oem.2010.061879

Ege M.J, Strachan D.P, Cookson W.O, Moffatt M.F, Gut I, Lathrop M, Kabesch M, Genuneit J, Buchele G, Sozanska B, Boznanski A, Cullinan P, Horak E, Bieli C, Braun-Fahrländer C, Heederik D, von Mutius E, GABRIELA Study Group. Gene-environment interaction for childhood asthma and exposure to farming in Central Europe. J Allergy Clin Immunol. 2011;127(1):138-144. DOI: 10.1016/j.jaci.2010.09.041

Loss G, Apprich S, Waser M, Kneifel W, Genuneit J, Buchele G, Weber J, Sozanska B, Danielewicz H, Horak E, van Neerven R.J, Heederik D, Lorenzen P.C, von Mutius E, Braun-Fahrländer C. The protective effect of farm milk consumption on childhood asthma and atopy: The GABRIELA study. J Allergy Clin Immunol. 2011;128(4):766-773.e4. DOI: 10.1016/j.jaci.2011.07.048

Ege M.J, Mayer M, Normand A.C, Genuneit J, Cookson W.O.C.M, Braun-Fahrländer C, Heederik D, Piarroux R, von Mutius E, GABRIELA Transregio 22 Study Group. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. 2011;364(8):701-709. DOI: 10.1056/NEJMoa1007302

Genuneit J, Büchele G, Waser M, Kovacs K, Debinska A, Boznanski A, Strunz-Lehner C, Horak E, Cullinan P, Heederik D, Braun-Fahrländer C, von Mutius E, GABRIELA Study Group. The GABRIEL Advanced Surveys: study design, participation and evaluation of bias. Paediatr Perinat Epidemiol. 2011;25(5):436-447. DOI: 10.1111/j.1365-3016.2011.01223.x

Moffatt M.F, Gut I.G, Demenais F, Strachan D.P, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson W.O, Imboden M, Liu L.J, Schindler C, Rochat T, Gerbase M, Curjuric I, Thun G.A, Probst-Hensch N, Braun-Fahrländer C. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363(13):1211-1221. DOI: 10.1056/NEJMoa0906312