Association of Body Mass Index and Parkinson Disease A Bidirectional Mendelian Randomization Study
Domenighetti, C. ; Puschmann, A. LU
; Hellberg, C.
LU
; Sharma, M.
LU
and Elbaz, A.
(2024)
In Neurology
103(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.MethodsWe 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... (More)
- 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.MethodsWe 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.ResultsSummary 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.DiscussionUsing 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. © American Academy of Neurology. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/57b8c872-e9c9-4732-b1a9-414b1ce06d4d
- author
- Domenighetti, C.
; Puschmann, A.
LU
; Hellberg, C.
LU
; Sharma, M.
LU
and Elbaz, A.
- author collaboration
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aged, Body Mass Index, Female, Genome-Wide Association Study, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Parkinson Disease, Polymorphism, Single Nucleotide, Risk Factors, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triacylglycerol, uric acid, adult, alcohol consumption, anxiety, Article, body mass, depression, disease duration, female, gene frequency, genetic liability, genome-wide association study, human, international parkinson disease genomics consortium, logistic regression analysis, major clinical study, male, Mendelian randomization analysis, neurosis, Parkinson disease, pleiotropy, prevalence, risk factor, single nucleotide polymorphism, aged, epidemiology, genetics, middle aged
- in
- Neurology
- volume
- 103
- issue
- 3
- article number
- e209620
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85198438116
- pmid:38986057
- ISSN
- 0028-3878
- DOI
- 10.1212/WNL.0000000000209620
- language
- English
- LU publication?
- yes
- id
- 57b8c872-e9c9-4732-b1a9-414b1ce06d4d
- date added to LUP
- 2024-09-03 14:22:54
- date last changed
- 2024-09-04 03:00:22
@article{57b8c872-e9c9-4732-b1a9-414b1ce06d4d,
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.MethodsWe 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.ResultsSummary 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.DiscussionUsing 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. © American Academy of Neurology.}},
author = {{Domenighetti, C. and Puschmann, A. and Hellberg, C. and Sharma, M. and Elbaz, A.}},
issn = {{0028-3878}},
keywords = {{Aged; Body Mass Index; Female; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Parkinson Disease; Polymorphism, Single Nucleotide; Risk Factors; high density lipoprotein cholesterol; low density lipoprotein cholesterol; triacylglycerol; uric acid; adult; alcohol consumption; anxiety; Article; body mass; depression; disease duration; female; gene frequency; genetic liability; genome-wide association study; human; international parkinson disease genomics consortium; logistic regression analysis; major clinical study; male; Mendelian randomization analysis; neurosis; Parkinson disease; pleiotropy; prevalence; risk factor; single nucleotide polymorphism; aged; epidemiology; genetics; middle aged}},
language = {{eng}},
number = {{3}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Neurology}},
title = {{Association of Body Mass Index and Parkinson Disease A Bidirectional Mendelian Randomization Study}},
url = {{http://dx.doi.org/10.1212/WNL.0000000000209620}},
doi = {{10.1212/WNL.0000000000209620}},
volume = {{103}},
year = {{2024}},
}