Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study

1. Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009; 373 : 1083–96. doi: 10.1016/S0140-6736(09)60318-4 19299006

2. Davey Smith G, Sterne JAC, Fraser A, Tynelius P, Lawlor DA, Rasmussen F. The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study. BMJ. 2009;339:b5043. doi: 10.1136/bmj.b5043 20028778

3. Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet. 2009;373 : 2055–66. doi: 10.1016/S0140-6736(09)60492-X 19524782

4. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385 : 117–71. doi: 10.1016/S0140-6736(14)61682-2 25530442

5. Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Giovannoni G, Lees AJ, et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol. 2012;72 : 893–901. doi: 10.1002/ana.23687 23071076

6. Noyce AJ, Lees AJ, Schrag A-E. The prediagnostic phase of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2016;87 : 871–8. doi: 10.1136/jnnp-2015-311890 26848171

7. van der Marck MA, Dicke HC, Uc EY, Kentin UC, Borm GF, Bloem BR, et al. Body mass index in Parkinson’s disease: a meta-analysis. Parkinsonism Relat Disord. 2012;18 : 263–7. doi: 10.1016/j.parkreldis.2011.10.016 22100523

8. Ma L, Zhang L, Gao XH, Chen W, Wu YP, Wang Y, et al. Dietary factors and smoking as risk factors for PD in a rural population in China: a nested case-control study. Acta Neurol Scand. 2006;113 : 278–81. doi: 10.1111/j.1600-0404.2005.00571.x 16542169

9. Chen H, Zhang SM, Schwarzschild MA, Hernán MA, Willett WC, Ascherio A. Obesity and the risk of Parkinson’s disease. Am J Epidemiol. 2004;159 : 547–55. 15003958

10. Qizilbash N, Gregson J, Johnson ME, Pearce N, Douglas I, Wing K, et al. Body mass index and risk of Parkinson’s disease in a cohort of two million people over two decades. Pharmacoepiol Drug Saf. 2016;25(Suppl 3):105.

11. Logroscino G, Sesso HD, Paffenbarger RS, Lee I-M. Body mass index and risk of Parkinson’s disease: a prospective cohort study. Am J Epidemiol. 2007;166 : 1186–90. doi: 10.1093/aje/kwm211 17709328

12. Hu G, Jousilahti P, Nissinen A, Antikainen R, Kivipelto M, Tuomilehto J. Body mass index and the risk of Parkinson disease. Neurology. 2006;67 : 1955–9. doi: 10.1212/01.wnl.0000247052.18422.e5 17159100

13. Wang Y-L, Wang Y-T, Li J-F, Zhang Y-Z, Yin H-L, Han B. Body mass index and risk of Parkinson’s disease: a dose-response meta-analysis of prospective studies. PLoS ONE. 2015;10(6):e0131778. doi: 10.1371/journal.pone.0131778 26121579

14. Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27 : 1133–63. doi: 10.1002/sim.3034 17886233

15. Noyce AJ, Nalls MA. Mendelian randomization—the key to understanding aspects of Parkinson’s disease causation? Mov Disord. 2015;31 : 478–83. doi: 10.1002/mds.26492 26695521

16. Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013;178 : 1177–84. doi: 10.1093/aje/kwt084 23863760

17. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518 : 197–206. doi: 10.1038/nature14177 25673413

18. Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet. 2014;46 : 989–93. doi: 10.1038/ng.3043 25064009

19. Johnson T. Efficient calculation for multi-SNP genetic risk scores. Vienna: Comprehensive R Archive Network; 2012 [cited 2016 Aug 1]. Available from: http://cran.r-project.org/web/packages/gtx/vignettes/ashg2012.pdf.

20. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44 : 512–25. doi: 10.1093/ije/dyv080 26050253

21. Brion MJA, Shakhbazov K, Visscher PM. Calculating statistical power in Mendelian randomization studies. Int J Epidemiol. 2013;42 : 1497–501. doi: 10.1093/ije/dyt179 24159078

22. Mayeda ER, Tchetgen EJ, Power MC, Weuve J, Jacqmin-Gadda H, Marden JR, et al. A simulation platform for quanitifying survival bias: an application to research on determinants of cognitive decline. Am J Epidemiol. 2016;184 : 378–87. doi: 10.1093/aje/kwv451 27578690

23. Driver JA, Logroscino G, Gaziano JM, Kurth T. Incidence and remaining lifetime risk of Parkinson disease in advanced age. Neurology. 2009;72 : 432–8. doi: 10.1212/01.wnl.0000341769.50075.bb 19188574

24. Kyrozis A, Ghika A, Stathopoulos P, Vassilopoulos D, Trichopoulos D, Trichopoulou A. Dietary and lifestyle variables in relation to incidence of Parkinson’s disease in Greece. Eur J Epidemiol. 2013;28 : 67–77. doi: 10.1007/s10654-012-9760-0 23377703

25. Driver JA, Smith A, Buring JE, Gaziano JM, Kurth T, Logroscino G. Prospective cohort study of type 2 diabetes and the risk of Parkinson’s disease. Diabetes Care. 2008;31 : 2003–5. doi: 10.2337/dc08-0688 18599528

26. Hsu CL, Voss MW, Best JR, Handy TC, Madden K, Bolandzadeh N, et al. Elevated body mass index and maintenance of cognitive function in late life: exploring underlying neural mechanisms. Front Aging Neurosci. 2015;7 : 155. doi: 10.3389/fnagi.2015.00155 26347646

27. Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol. 2004;3 : 169–78. doi: 10.1016/S1474-4422(04)00681-7 14980532

28. De Pablo-Fernández E, Breen DP, Bouloux PM, Barker RA, Foltynie T, Warner TT. Neuroendocrine abnormalities in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2017;88(2):176–85. doi: 10.1136/jnnp-2016-314601 27799297

29. Howells DW, Porritt MJ, Wong JYF, Batchelor PE, Kalnins R, Hughes AJ, et al. Reduced BDNF mRNA expression in the Parkinson’s disease substantia nigra. Exp Neurol. 2000;166 : 127–35. doi: 10.1006/exnr.2000.7483 11031089

30. Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011;10 : 209–19. doi: 10.1038/nrd3366 21358740

31. BDNF Study Group. A controlled trial of recombinant methionyl human BDNF in ALS: the BDNF Study Group (phase III). Neurology. 1999;52 : 1427–33. 10227630

32. Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015;85 : 257–73. doi: 10.1016/j.neuron.2014.12.007 25611507

33. Bové J, Martínez-Vicente M, Vila M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat Rev Neurosci. 2011;12 : 437–52. doi: 10.1038/nrn3068 21772323

34. Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, et al. Physical activities and future risk of Parkinson disease. Neurology. 2010;75 : 341–8. doi: 10.1212/WNL.0b013e3181ea1597 20660864

35. Pontzer H, Durazo-Arvizu R, Dugas LR, PLange-Rhule J, Bovet P, Forrester TE, et al. Constrained total energy expenditure and metabolic adaptation to physical activity in adult humans. Curr Biol. 2016;26 : 410–7. doi: 10.1016/j.cub.2015.12.046 26832439

36. Richmond RC, Davey Smith G, Ness AR, den Hoed M, McMahon G, Timpson NJ. Assessing causality in the association between child adiposity and physical activity levels: a Mendelian randomization analysis. PLoS Med. 2014;11(3):e1001618. doi: 10.1371/journal.pmed.1001618 24642734

37. Østergaard SD, Mukherjee S, Sharp SJ, Proitsi P, Lotta LA, Day F, et al. Associations between potentially modifiable risk factors and Alzheimer disease: a Mendelian randomization study. PLoS Med. 2015;12(6):e1001841. doi: 10.1371/journal.pmed.1001841 26079503

38. Lawlor DA. Commentary: two-sample Mendelian randomization: opportunities and challenges. Int J Epidemiol. 2016;43(3):908–15.

39. Tyrrell J, Jones SE, Beaumont R, Astley CM, Lovell R, Yaghootkar H, et al. Height, body mass index, and socioeconomic status: Mendelian randomisation study in UK Biobank. BMJ. 2016;352:i582. doi: 10.1136/bmj.i582 26956984

40. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3):e1001779. doi: 10.1371/journal.pmed.1001779 25826379

41. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body fatness and cancer—viewpoint of the IARC working group. N Engl J Med. 2016;375 : 794–8. doi: 10.1056/NEJMsr1606602 27557308

42. Holmes MV, Dale CE, Zuccolo L, Silverwood RJ, Guo Y, Ye Z, et al. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014;349:g4164. doi: 10.1136/bmj.g4164 25011450