Association of Body Mass Index and Parkinson Disease

Domenighetti, Cloé ; Sugier, Pierre-Emmanuel; Ashok Kumar Sreelatha, Ashwin; Schulte, Claudia ; Grover, Sandeep ; Portugal, Berta ; Lee, Pei-Chen ; May, Patrick ; Bobbili, Dheeraj; Radivojkov Blagojevic, Milena; Lichtner, Peter; Singleton, Andrew B. ; Hernandez, Dena; Edsal, Connor ; Mellick, George D. ; Zimprich, Alexander A.; Pirker, Walter ; Rogaeva, Ekaterina A. ; Lang, Anthony E. ; Koks, Sulev ; Taba, Pille; Lesage, Suzanne ; Brice, Alexis ; Corvol, Jean-Christophe ; Chartier-Harlin, Marie-Christine; Mutez, Eugenie; Brockmann, Kathrin ; Deutschlander, Angela B. ; Hadjigeorgiou, Georgios M. ; Dardiotis, Efthimios ; Stefanis, Leonidas; Simitsi, Athina Maria; Valente, Enza Maria ; Petrucci, Simona; Straniero, Letizia ; Zecchinelli, Anna L.; 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; Warrenburg, Bart P.C. Van De ; Bloem, Bastiaan R. ; Toft, Mathias ; Pihlstrøm, Lasse ; Correia Guedes, Leonor; Ferreira, Joaquim J. ; Bardien, Soraya ; Carr, Jonathan ; Tolosa, Eduardo ; Ezquerra, Mario ; Pastor, Pau ; Diez-Fairen, Monica ; Wirdefeldt, Karin; Pedersen, Nancy L. ; Ran, Caroline ; Belin, Andrea C. ; Puschmann, Andreas ; Hellberg, Clara; Clarke, Carl E. ; Morrison, Karen E. ; Tan, Manuela M. ; Krainc, Dimitri ; Burbulla, Lena F. ; Farrer, Matthew ; Kruger, Rejko ; Gasser, Thomas; Sharma, Manu und Elbaz, Alexis (2024): Association of Body Mass Index and Parkinson Disease. In: Neurology, Bd. 103, Nr. 3

Abstract

Background and Objectives : The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. Methods : We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. Results : Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70–0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55–0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62–0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74–0.99], p = 0.032) than men (ORIVW 0.92 [0.80–1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. Discussion : Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0028-3878
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198