PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Witoelar, A.W.* ; Jansen, I.E.* ; Wang, Y.* ; Desikan, R.S.* ; Gibbs, J.R.* ; Blauwendraat, C.* ; Thompson, W.K.* ; Hernandez, D.G.* ; Djurovic, S.* ; Schork, A.J.* ; Bettella, F.* ; Ellinghaus, D.* ; Franke, A.* ; Lie, B.A.* ; McEvoy, L.K.* ; Karlsen, T.H.* ; Lesage, S.* ; Morris, H.R.* ; Brice, A.* ; Wood, N.W.* ; Heutink, P.* ; Hardy, J.* ; Singleton, A.B.* ; Dale, A.M.* ; Gasser, T.* ; Andreassen, O.A.* ; Sharma, M.* ; Nalls, M.A.* ; Plagnol, V.* ; Sheerin, U.M.* ; Saad, M.* ; Simon-Sanchez, J.* ; Schulte, C.* ; Sveinbjörnsdóttir, S.* ; Arepalli, S.* ; Barker, R.A.* ; Ben-Shlomo, Y.* ; Berendse, H.W.* ; Berg, D.* ; Bhatia, K.P.* ; de Bie, R.M.A.* ; Biffi, A.* ; Bloem, B.* ; Bochdanovits, Z.* ; Bonin, M.* ; Bras, J.M.* ; Brockmann, K.* ; Brooks, J.M.* ; Burn, D.J.* ; Majounie, E.* ; Illig, T. ; Lichtner, P. ; Weale, M.E.*

Genome-wide pleiotropy between Parkinson disease and autoimmune diseases.

JAMA Neurol. 74, 780-792 (2017)
Verlagsversion DOI
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
IMPORTANCE: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. OBJECTIVES: To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. DESIGN, SETTING, AND PARTICIPANTS: Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. MAIN OUTCOMES AND MEASURES: The primary outcomewas a list of novel loci and their pathways involved in PD and autoimmune diseases. RESULTS: Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes inmethylation or expression levels of adjacent genes. CONCLUSIONS AND RELEVANCE: The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
10.029
2.379
4
144
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2168-6149
e-ISSN 2168-6157
Zeitschrift JAMA neurology
Quellenangaben Band: 74, Heft: 7, Seiten: 780-792 Artikelnummer: , Supplement: ,
Verlag American Medical Association
Verlagsort Chicago, Ill.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-001
G-500700-001
DOI 10.1001/jamaneurol.2017.0469
Scopus ID 85024384526
Erfassungsdatum 2017-09-21
[➜Korrektur melden]