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NPJ Parkinson's disease · 2026

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

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Vincze Katalin, Szwajda Agnieszka, Ploner Alexander, Karlsson Robert, Kang Xiaoying, Tang Bowen, Qin Chenxi, Domenighetti Cloé, Sugier Pierre-Emmanuel, Ashok Kumar Sreelatha Ashwin, Schulte Claudia, Portugal Berta, May Patrick, Bobbili Dheeraj Reddy, Radivojkov-Blagojevic Milena, Lichtner Peter, Singleton Andrew B, Hernandez Dena G, Edsall Connor, Mellick George D, Zimprich Alexander, Pirker Walter, Rogaeva Ekaterina, Lang Anthony E, Koks Sulev, Taba Pille, Lesage Suzanne, Brice Alexis, Corvol Jean-Christophe, Chartier-Harlin Marie-Christine, Mutez Eugénie, Brockmann Kathrin, Deutschlander Angela B, Burbulla Lena F, Hadjigeorgiou Georges M, Dardiotis Efthimos, Stefanis Leonidas, Simitsi Athina Maria, Valente Enza Maria, Petrucci Simona, Straniero Letizia, Zecchinelli Anna, Pezzoli Gianni, Brighina Laura, Ferrarese Carlo, Annesi Grazia, Quattrone Andrea, Gagliardi Monica, Matsuo Hirotaka, Nakayama Akiyoshi, Hattori Nobutaka, Nishioka Kenya, Chung Sun Ju, Kim Yun Joong, Kolber Pierre, Van de Warrenburg Bart Pc, Bloem Bastiaan R, Toft Mathias, Pihlstrøm Lasse, Correia Guedes Leonor, Ferreira Joaquim J, Bardien Soraya, Carr Jonathan, Tolosa Eduardo, Ezquerra Mario, Pastor Pau, Ran Caroline, Belin Andrea C, Puschmann Andreas, Clarke Carl E, Morrison Karen E, Tan Manuela, Krainc Dimitri, Farrer Matt J, Landoulsi Zied, Kruger Rejko, Gasser Thomas, Elbaz Alexis, Sharma Manu, Pedersen Nancy L, Carlsson Sofia, Hägg Sara, Wirdefeldt Karin, Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (COURAGE-PD) Consortium, Domenighetti Cloé, Sugier Pierre-Emmanuel, Ashok Kumar Sreelatha Ashwin, Schulte Claudia, Portugal Berta, May Patrick, Bobbili Dheeraj Reddy, Radivojkov-Blagojevic Milena, Lichtner Peter, Singleton Andrew B, Hernandez Dena G, Edsall Connor, Mellick George D, Zimprich Alexander, Pirker Walter, Rogaeva Ekaterina, Lang Anthony E, Koks Sulev, Taba Pille, Lesage Suzanne, Brice Alexis, Corvol Jean-Christophe, Chartier-Harlin Marie-Christine, Mutez Eugénie, Brockmann Kathrin, Deutschlander Angela B, Burbulla Lena F, Hadjigeorgiou Georges M, Dardiotis Efthimos, Stefanis Leonidas, Simitsi Athina Maria, Valente Enza Maria, Petrucci Simona, Straniero Letizia, Zecchinelli Anna, Pezzoli Gianni, Brighina Laura, Ferrarese Carlo, Annesi Grazia, Quattrone Andrea, Gagliardi Monica, Matsuo Hirotaka, Nakayama Akiyoshi, Hattori Nobutaka, Nishioka Kenya, Chung Sun Ju, Kim Yun Joong, Kolber Pierre, Van de Warrenburg Bart Pc, Bloem Bastiaan R, Toft Mathias, Pihlstrøm Lasse, Correia Guedes Leonor, Ferreira Joaquim J, Bardien Soraya, Carr Jonathan, Tolosa Eduardo, Ezquerra Mario, Pastor Pau, Ran Caroline, Belin Andrea C, Puschmann Andreas, Clarke Carl E, Morrison Karen E, Tan Manuela, Krainc Dimitri, Farrer Matt J, Landoulsi Zied, Kruger Rejko, Gasser Thomas, Elbaz Alexis, Sharma Manu, Wirdefeldt Karin

Аннотация

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.

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

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