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General and abdominal adiposity and the risk of Parkinson's disease: A prospective cohort study
INTRODUCTION: Due to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD. METHODS: In 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking. RESULTS: We found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD. CONCLUSION: Our data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking. ; This research has been made possible thanks to a grant of the European Community (5th Framework Programme) to Prof. Paolo Vineis (grant QLK4CT199900927); and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from founders. Mortality data from the Netherlands are obtained from "Statistics Netherlands". The centers contributing to the NeuroEPIC4PD study are financially supported by: Europe Against Cancer Program of the European Commission (SANCO); ISCIII, Red de Centros RCESP, C03/09; Spanish Ministry of Health (ISCIII RETICC RD06/0020); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Spanish Ministry of Health (ISCIII RETICC RD06/0020) Cancer Research U.K.; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; Welcome Trust, United Kingdom Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Foundation; Swedish Scientific Council; Regional Governments of Skåne and Västerbotten Counties, Sweden; Norwegian Cancer Society; Research Council of Norway; French League against cancer, Inserm, Mutuelle Generale l'Education National and IGR; the Hellenic Health Foundation.
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Exploring causality of the association between smoking and Parkinson's disease
BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking 30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect. ; Mortality data from the Netherlands are obtained from "Statistics Netherlands". In addition we would like to thank for their financial support: Europe Against cancer Program of the European Commission (SANCO); ISCIII, Red de Centros RCESP, C03/09; Spanish Ministry of Health (ISCIII RETICC RD06/0020); Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Spanish Ministry of Health (ISCIII RETICC RD06/0020)Cancer Research U.K.; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; National Institute of Health Research funding of a Biomedical Research Centre in Cambridge ; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; Wellcome Trust, United Kingdom Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer; Swedish Research Council; European Research Council, Regional Government of Skåne and Västerbotten, Sweden; Norwegian Cancer Society; Research Council of Norway; French League against cancer, Inserm, Mutuelle Generale l'Education National and IGR. Claudio Ruffmann received funding from 'Fondazione Grigioni per la lotta al Morbo di Parkinson
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
In: Gao , Y , Wang , T , Yu , X , Ferrari , R , Hernandez , D G , Nalls , M A , Rohrer , J D , Ramasamy , A , Kwok , J B J , Dobson-Stone , C , Brooks , W S , Schofield , P R , Halliday , G M , Hodges , J R , Piguet , O , Bartley , L , Thompson , E , Haan , E , Hernández , I , Ruiz , A , Boada , M , Borroni , B , Padovani , A , Cruchaga , C , Cairns , N J , Benussi , L , Binetti , G , Ghidoni , R , Forloni , G , Albani , D , Galimberti , D , Fenoglio , C , Serpente , M , Scarpini , E , Clarimón , J , Lleó , A , Blesa , R , Waldö , M L , Nilsson , K , Nilsson , C , Mackenzie , I R A , Hsiung , G Y R , Mann , D M A , Grafman , J , Morris , C M , Attems , J , Griffiths , T D , McKeith , I G , Thomas , A J , Pietrini , P , Huey , E D , Wassermann , E M , Baborie , A , Jaros , E , Tierney , M C , Pastor , P , Razquin , C , Ortega-Cubero , S , Alonso , E , Perneczky , R , Diehl-Schmid , J , Alexopoulos , P , Kurz , A , Rainero , I , Rubino , E , Pinessi , L , Rogaeva , E , George-Hyslop , P S , Rossi , G , Tagliavini , F , Giaccone , G , Rowe , J B , Schlachetzki , J C M , Uphill , J , Collinge , J , Mead , S , Danek , A , Van Deerlin , V M , Grossman , M , Trojanowski , J Q , van der Zee , J , Cruts , M , Van Broeckhoven , C , Cappa , S F , Leber , I , Hannequin , D , Golfier , V , Vercelletto , M , Brice , A , Nacmias , B , Sorbi , S , Bagnoli , S , Piaceri , I , Nielsen , J E , Hjermind , L E , Riemenschneider , M , Mayhaus , M , Ibach , B , Gasparoni , G , Pichler , S , Gu , W , Rossor , M N , Fox , N C , Warren , J D , Spillantini , M G , Morris , H R , Rizzu , P , Heutink , P , Snowden , J S , Rollinson , S , Richardson , A , Gerhard , A , Bruni , A C , Maletta , R , Frangipane , F , Cupidi , C , Bernardi , L , Anfossi , M , Gallo , M , Conidi , M E , Smirne , N , Rademakers , R , Baker , M , Dickson , D W , Graff-Radford , N R , Petersen , R C , Knopman , D , Josephs , K A , Boeve , B F , Parisi , J E , Seeley , W W , Miller , B L , Karydas , A M , Rosen , H , van Swieten , J C , Dopper , E G P , Seelaar , H , Pijnenburg , Y A L , Scheltens , P , Logroscino , G , Capozzo , R , Novelli , V , Puca , A A , Franceschi , M , Postiglione , A , Milan , G , Sorrentino , P , Kristiansen , M , Chiang , H H , Graff , C , Pasquier , F , Rollin , A , Deramecourt , V , Lebouvier , T , Kapogiannis , D , Ferrucci , L , Pickering-Brown , S , Singleton , A B , Hardy , J , Momeni , P , Zhao , H , Zeng , P & International FTD-Genomics Consortium (IFGC) 2020 , ' Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis ' , Scientific Reports , vol. 10 , no. 1 , 12184 . https://doi.org/10.1038/s41598-020-68848-9
We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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