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Vincze, K.* ; Szwajda, A.* ; Ploner, A.* ; Karlsson, R.* ; Kang, X.* ; Tang, B.* ; Qin, C.* ; Domenighetti, C.* ; Sugier, P.* ; Sreelatha, A.A.K.* ; Schulte, C.* ; Portugal, B.* ; May, P.* ; Bobbili, D.R.* ; Radivojkov-Blagojevic, M. ; Lichtner, P. ; Singleton, A.B.* ; Hernandez, D.G.* ; Edsall, C.* ; Mellick, G.D.* ; Zimprich, A.* ; Pirker, W.* ; Rogaeva, E.* ; Lang, A.E.* ; Koks, S.* ; Taba, P.* ; Lesage, S.* ; Brice, A.* ; Corvol, J.* ; Chartier-Harlin, M.* ; Mutez, E.* ; Brockmann, K.* ; Deutschländer, A.* ; Burbulla, L.F.* ; Hadjigeorgiou, G.* ; Dardiotis, E.* ; Stefanis, L.* ; Simitsi, A.M.* ; Valente, E.P.* ; Petrucci, S.* ; Straniero, L.* ; Zecchinelli, A.* ; Pezzoli, G.* ; Brighina, L.* ; Ferrarese, C.* ; Annesi, G.* ; Quattrone, A.* ; Gagliardi, M.* ; Matsuo, H.* ; Nakayama, A.* ; Hattori, N.* ; Nishioka, K.* ; Chung, S.J.* ; Kim, Y.W.* ; Kolber, P.* ; Warrenburg, B.P.v.d.* ; Bloem, B.R.* ; Toft, M.* ; Pihlstrøm, L.* ; Guedes, L.C.* ; Ferreira, J.J.* ; Bardien, S.* ; Carr, J.* ; Tolosa, E.* ; Ezquerra, M.* ; Pástor, P.* ; Ran, C.* ; Belin, A.C.* ; Puschman, A.* ; Clarke, D.C.E.* ; Morrison, K.* ; Tan, M.* ; Krainc, D.* ; Farrer, M.J.* ; Landoulsi, Z.* ; Kruger, R.* ; Gasser, T.* ; Elbaz, A.* ; Sharma, M.* ; Pedersen, N.L.* ; Carlsson, S.* ; Hägg, S.* ; Wirdefeldt, K.*

Genetic variation in antidiabetic drug targets: Associations with Parkinson’s disease risk and age at onset.

npj Parkinsons Dis. 12:127 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
To investigate whether antidiabetic drugs have a biological basis to be repurposed in PD prevention, we applied a drug target Mendelian randomization framework to assess associations between genetic variation in antidiabetic drug targets and PD risk or age at onset (AAO). Instrumental variables (IVs) were derived from GWAS summary statistics on fasting glucose (FG), glycated hemoglobin (HbA1c), and gene expression data from GTEx. Apart from SGLT2 inhibitors, all other antidiabetic drugs of interest could be instrumented through our methods. Positive and negative control analyses were carried out to validate 20 IVs in the FG arm and 23 IVs in the HbA1c arm. DPP-4 inhibitors failed the positive control. GWAS summary statistics for PD risk and AAO data were sourced from the IPDGC and COURAGE-PD consortia, resulting in 42 083 cases/457 090 controls for risk and 37 103 PD cases for AAO. MR analyses showed no significant associations across consortia or in meta-analysis. These findings do not support a causal role of genetic variation in antidiabetic drug targets in PD risk or AAO.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mendelian Randomization ; Drug ; Genome-wide Association Study ; Glycated Hemoglobin ; Diabetes Mellitus ; Disease ; Genetic Variation ; Genetic Association; Insights
ISSN (print) / ISBN 2373-8057
e-ISSN 2373-8057
Journal npj Parkinson's Disease
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 127 Supplement: ,
Publisher Springer
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Grants Grants from the Swedish state under the agreement between the Swedish government and the county councils
Parkinsonfonden
Vetenskapsrådet