Genetic variants linked to higher BMI may be protective against Parkinson disease

Genetic variants linked to higher body mass index (BMI) are associated with lower risk of Parkinson disease, according to a study published by Nicholas Wood and colleagues from the University College London, UK, in PLOS Medicine.

The researchers used a Mendelian randomization approach to examine whether genetic variants linked to higher BMI were also associated with risk of Parkinson disease. The associations between the genetic variants and BMI were obtained from the GIANT consortium and the relationship between the same genetic variants and Parkinson disease was ascertained from a recent meta-analysis that included 13,708 cases of Parkinson disease and 95,282 controls. The researchers observed that genetic risk expected to confer a lifetime exposure of 5-kg/m2 higher BMI was associated with an 18% lower risk of Parkinson disease (OR 0.82, 95% CI 0.69-0.98). A limitation of the approach is that individuals who have higher BMI have a higher risk of earlier mortality, and therefore individuals with lower BMI may be over-represented amongst individuals diagnosed with Parkinson disease. This "frailty effect" could at least partially account for the estimated association.

The authors say: "Although our results suggest that higher BMI is potentially protective against PD, the negative health impacts of raising BMI are likely to be significant, and should be taken into account."

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The authors received no specific funding for this work. Other individual financial disclosures: AJN is funded by Parkinson's UK (ref F1201). DAK is supported by an MB PhD Award from the International Journal of Experimental Pathology. GH, PCH, GDS and DAL work in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_1201/1 and MC_UU_1201/5). DAL is a National Institute of Health Research Senior Investigator (NF-SI-0166-10196). PCH is supported by CRUK Population Research Postdoctoral Fellowship C52724/A20138. PAL receives funding from the MRC (MR/N026004/1 and MR/L010933/1). MN, ASi, AN and TRP participation in this study was supported in part by the Intramural Research Program of the National Institute on Aging, NIH. University College London Hospitals and University College London receive support from the Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres (BRC). NWW is an NIHR senior Investigator and receives support from the JPND-MRC Comprehensive Unbiased Risk factor Assessment for Genetics and Environment in Parkinson's disease (COURAGE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

AJN reports: grants from Parkinson's UK, Élan/Prothena Pharmaceuticals, GE Healthcare; shares in LifeLab Ltd; advisory board membership for myHealthPal; honoraria from Office Octopus, Henry Stewart Talks, and Britannia Pharmaceuticals Ltd, all outside of the submitted work. PAL reports grants from MRC, BBSRC, National Institutes of Health, Michael J. Fox Foundation, personal fees from Astex Pharmaceuticals, outside the submitted work. TF reports grants from Michael J Fox Foundation, grants from Brain Research Trust, grants from European Union FP7, grants from John Black Charitable Foundation, personal fees from Medtronic, personal fees from BIAL, personal fees from Profile Pharma, personal fees from Brittania, all outside the submitted work. ASc reports grants from GE Healthcare, outside the submitted work. AJL reports personal fees from Britannia Pharmaceuticals Ltd, BIAL Portela, Profile Pharma Ltd, Teva, Lundbeck, Roche, UCB, NeuroDerm, Nordicinfu Care, Decision Resources, all outside of the submitted work. GDS is a member of the Editorial Board of PLOS Medicine. Mike Nalls participated in this work as a paid contractor/consultant for Kelly Government Services. DAL reports grants from UK Medical Research Council, during the conduct of the study; grants from Medical Research council, grants from Wellcome Trust, grants from European Research Council, grants from Roche Diagnostics, grants from Medtronic, grants from Ferring Pharmaceuticals, outside the submitted work. DAK, GH, ASi, AN, EDP-F, JH, NP, TRP, NWW, MN report no relevant disclosures.

Noyce AJ, Kia DA, Hemani G, Nicolas A, Price TR, De Pablo-Fernandez E, et al. (2017) Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study. PLoS Med 14(6): e1002314. https://doi.org/10.1371/journal.pmed.1002314

Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, United Kingdom
Centre for Neuroscience and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
Laboratory for Neurogenetics, National Institute on Aging National Institutes of Health, Bethesda, Maryland, United States of America
School of Pharmacy, University of Reading, Reading, United Kingdom
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, United Kingdom
Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, London, United Kingdom
Data Technica International, Glen Echo, Maryland, United States of America
Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, United Kingdom

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