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000270631 1001_ $$00000-0001-6408-0351$$aDomenighetti, Cloé$$b0
000270631 245__ $$aAssociation of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.
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000270631 520__ $$aThe 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.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.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.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.
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000270631 650_2 $$2MeSH$$aHumans
000270631 650_2 $$2MeSH$$aMendelian Randomization Analysis
000270631 650_2 $$2MeSH$$aParkinson Disease: genetics
000270631 650_2 $$2MeSH$$aParkinson Disease: epidemiology
000270631 650_2 $$2MeSH$$aBody Mass Index
000270631 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide: genetics
000270631 650_2 $$2MeSH$$aFemale
000270631 650_2 $$2MeSH$$aMale
000270631 650_2 $$2MeSH$$aGenome-Wide Association Study
000270631 650_2 $$2MeSH$$aMiddle Aged
000270631 650_2 $$2MeSH$$aAged
000270631 650_2 $$2MeSH$$aRisk Factors
000270631 7001_ $$aSugier, Pierre-Emmanuel$$b1
000270631 7001_ $$aAshok Kumar Sreelatha, Ashwin$$b2
000270631 7001_ $$0P:(DE-2719)9000366$$aSchulte, Claudia$$b3
000270631 7001_ $$00000-0003-2615-4916$$aGrover, Sandeep$$b4
000270631 7001_ $$00000-0001-7603-6104$$aPortugal, Berta$$b5
000270631 7001_ $$00000-0001-7813-0823$$aLee, Pei-Chen$$b6
000270631 7001_ $$00000-0001-8698-3770$$aMay, Patrick$$b7
000270631 7001_ $$aBobbili, Dheeraj$$b8
000270631 7001_ $$aRadivojkov Blagojevic, Milena$$b9
000270631 7001_ $$aLichtner, Peter$$b10
000270631 7001_ $$00000-0001-5606-700X$$aSingleton, Andrew B$$b11
000270631 7001_ $$aHernandez, Dena$$b12
000270631 7001_ $$00000-0001-6876-1496$$aEdsall, Connor$$b13
000270631 7001_ $$00000-0002-7211-4651$$aMellick, George D$$b14
000270631 7001_ $$aZimprich, Alexander A$$b15
000270631 7001_ $$00000-0002-9729-9728$$aPirker, Walter$$b16
000270631 7001_ $$00000-0002-2852-0329$$aRogaeva, Ekaterina A$$b17
000270631 7001_ $$00000-0003-1229-3667$$aLang, Anthony E$$b18
000270631 7001_ $$00000-0001-6087-6643$$aKoks, Sulev$$b19
000270631 7001_ $$aTaba, Pille$$b20
000270631 7001_ $$00000-0003-4158-2601$$aLesage, Suzanne$$b21
000270631 7001_ $$00000-0002-0941-3990$$aBrice, Alexis$$b22
000270631 7001_ $$00000-0001-7325-0199$$aCorvol, Jean-Christophe$$b23
000270631 7001_ $$aChartier-Harlin, Marie-Christine$$b24
000270631 7001_ $$aMutez, Eugenie$$b25
000270631 7001_ $$0P:(DE-2719)2811916$$aBrockmann, Kathrin$$b26
000270631 7001_ $$00000-0003-2152-9926$$aDeutschlander, Angela B$$b27
000270631 7001_ $$00000-0001-5386-4273$$aHadjigeorgiou, Georgios M$$b28
000270631 7001_ $$00000-0003-2957-641X$$aDardiotis, Efthimios$$b29
000270631 7001_ $$aStefanis, Leonidas$$b30
000270631 7001_ $$aSimitsi, Athina Maria$$b31
000270631 7001_ $$00000-0002-0600-6820$$aValente, Enza Maria$$b32
000270631 7001_ $$aPetrucci, Simona$$b33
000270631 7001_ $$00000-0002-1733-7561$$aStraniero, Letizia$$b34
000270631 7001_ $$aZecchinelli, Anna L$$b35
000270631 7001_ $$00000-0003-4665-6710$$aPezzoli, Gianni$$b36
000270631 7001_ $$00000-0002-3967-0541$$aBrighina, Laura$$b37
000270631 7001_ $$aFerrarese, Carlo$$b38
000270631 7001_ $$00000-0001-9951-8798$$aAnnesi, Grazia$$b39
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000270631 7001_ $$00000-0002-3386-9808$$aGagliardi, Monica$$b41
000270631 7001_ $$aMatsuo, Hirotaka$$b42
000270631 7001_ $$00000-0002-6654-0726$$aNakayama, Akiyoshi$$b43
000270631 7001_ $$00000-0002-2034-2556$$aHattori, Nobutaka$$b44
000270631 7001_ $$00000-0001-8607-9757$$aNishioka, Kenya$$b45
000270631 7001_ $$00000-0003-4118-8233$$aChung, Sun Ju$$b46
000270631 7001_ $$00000-0002-2956-1552$$aKim, Yun Joong$$b47
000270631 7001_ $$aKolber, Pierre$$b48
000270631 7001_ $$00000-0003-4412-1616$$aVan De Warrenburg, Bart P C$$b49
000270631 7001_ $$00000-0002-6371-3337$$aBloem, Bastiaan R$$b50
000270631 7001_ $$00000-0002-6723-6865$$aToft, Mathias$$b51
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000270631 7001_ $$aCorreia Guedes, Leonor$$b53
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000270631 7001_ $$00000-0003-0216-5717$$aMorrison, Karen E$$b68
000270631 7001_ $$00000-0001-5835-669X$$aTan, Manuela M$$b69
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000270631 7001_ $$00000-0001-9724-5490$$aElbaz, Alexis$$b76
000270631 7001_ $$aGenetics, Comprehensive Unbiased Risk Factor Assessment for$$b77
000270631 7001_ $$aDisease, Environment in Parkinson's$$b78$$eCollaboration Author
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