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@ARTICLE{Domenighetti:270631,
author = {Domenighetti, Cloé and Sugier, Pierre-Emmanuel and Ashok
Kumar Sreelatha, Ashwin and Schulte, Claudia and Grover,
Sandeep and Portugal, Berta and Lee, Pei-Chen and May,
Patrick and Bobbili, Dheeraj and Radivojkov Blagojevic,
Milena and Lichtner, Peter and Singleton, Andrew B and
Hernandez, Dena and Edsall, Connor and Mellick, George D and
Zimprich, Alexander A and Pirker, Walter and Rogaeva,
Ekaterina A and Lang, Anthony E and Koks, Sulev and Taba,
Pille and Lesage, Suzanne and Brice, Alexis and Corvol,
Jean-Christophe and Chartier-Harlin, Marie-Christine and
Mutez, Eugenie and Brockmann, Kathrin and Deutschlander,
Angela B and Hadjigeorgiou, Georgios M and Dardiotis,
Efthimios and Stefanis, Leonidas and Simitsi, Athina Maria
and Valente, Enza Maria and Petrucci, Simona and Straniero,
Letizia and Zecchinelli, Anna L and Pezzoli, Gianni and
Brighina, Laura and Ferrarese, Carlo and Annesi, Grazia and
Quattrone, Andrea and Gagliardi, Monica and Matsuo, Hirotaka
and Nakayama, Akiyoshi and Hattori, Nobutaka and Nishioka,
Kenya and Chung, Sun Ju and Kim, Yun Joong and Kolber,
Pierre and Van De Warrenburg, Bart P C and Bloem, Bastiaan R
and Toft, Mathias and Pihlstrøm, Lasse and Correia Guedes,
Leonor and Ferreira, Joaquim J and Bardien, Soraya and Carr,
Jonathan and Tolosa, Eduardo and Ezquerra, Mario and Pastor,
Pau and Diez-Fairen, Monica and Wirdefeldt, Karin and
Pedersen, Nancy L and Ran, Caroline and Belin, Andrea C and
Puschmann, Andreas and Hellberg, Clara and Clarke, Carl E
and Morrison, Karen E and Tan, Manuela M and Krainc, Dimitri
and Burbulla, Lena F. and Farrer, Matthew and Krüger, Rejko
and Gasser, Thomas and Sharma, Manu and Elbaz, Alexis and
Genetics, Comprehensive Unbiased Risk Factor Assessment for},
collaboration = {Disease, Environment in Parkinson's},
title = {{A}ssociation of {B}ody {M}ass {I}ndex and {P}arkinson
{D}isease: {A} {B}idirectional {M}endelian {R}andomization
{S}tudy.},
journal = {Neurology},
volume = {103},
number = {3},
issn = {0028-3878},
address = {[Erscheinungsort nicht ermittelbar]},
publisher = {Ovid},
reportid = {DZNE-2024-00803},
pages = {e209620},
year = {2024},
abstract = {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.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.},
keywords = {Humans / Mendelian Randomization Analysis / Parkinson
Disease: genetics / Parkinson Disease: epidemiology / Body
Mass Index / Polymorphism, Single Nucleotide: genetics /
Female / Male / Genome-Wide Association Study / Middle Aged
/ Aged / Risk Factors},
cin = {AG Gasser / AG Burbulla},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)5000074},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38986057},
doi = {10.1212/WNL.0000000000209620},
url = {https://pub.dzne.de/record/270631},
}