المؤلفون: Domenighetti C., Sugier P.-E., Sreelatha A.A.K., Schulte C., Grover S., Mohamed O., Portugal B., May P., Bobbili D.R., Radivojkov-Blagojevic M., Lichtner P., Singleton A.B., Hernandez D.G., Edsall C., Mellick G.D., Zimprich A., Pirker W., Rogaeva E., Lang A.E., Koks S., Taba P., Lesage S., Brice A., Corvol J.-C., Chartier-Harlin M.-C., Mutez E., Brockmann K., Deutschländer A.B., Hadjigeorgiou G.M., Dardiotis E., Stefanis L., Simitsi A.M., Valente E.M., Petrucci S., Duga S., Straniero L., Zecchinelli A., Pezzoli G., Brighina L., Ferrarese C., Annesi G., Quattrone A., Gagliardi M., Matsuo H., Kawamura Y., Hattori N., Nishioka K., Chung S.J., Kim Y.J., Kolber P., Van De Warrenburg B.P.C., Bloem B.R., Aasly J., Toft M., Pihlstrøm L., Guedes L.C., Ferreira J.J., Bardien S., Carr J., Tolosa E., Ezquerra M., Pastor P., Diez-Fairen M., Wirdefeldt K., Pedersen N.L., Ran C., Belin A.C., Puschmann A., Hellberg C., Clarke C.E., Morrison K.E., Tan M., Krainc D., Burbulla L.F., Farrer M.J., Krüger R., Gasser T., Sharma M., Elbaz A.

المصدر: Journal of Parkinson's Disease ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123813753&doi=10.3233%2fJPD-212851&partnerID=40&md5=bb722d2b2f2b7e79ffdcb4417ba894c4Test

مصطلحات موضوعية: aged, ancestry group, Article, case control study, coffee consumption, cohort analysis, controlled study, disease duration, drinking behavior, genetic polymorphism, genetic variability, genome-wide association study, human, incidence, lifestyle modification, major clinical study, Mendelian randomization analysis, observational study, Parkinson disease, patient participation, pleiotropy, prevalence, sample size, smoking, survival rate, coffee, epidemiology, genetics, risk factor, Alcohol Drinking

الوصف: Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants =67 years old and cases with disease duration =7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power. © 2022 - IOS Press. All rights reserved.

العلاقة: http://hdl.handle.net/11615/73411Test

الإتاحة: https://doi.org/10.3233/JPD-212851Test
http://hdl.handle.net/11615/73411Test

المؤلفون: Domenighetti C., Sugier P.-E., Ashok Kumar Sreelatha A., Schulte C., Grover S., Mohamed O., Portugal B., May P., Bobbili D.R., Radivojkov-Blagojevic M., Lichtner P., Singleton A.B., Hernandez D.G., Edsall C., Mellick G.D., Zimprich A., Pirker W., Rogaeva E., Lang A.E., Koks S., Taba P., Lesage S., Brice A., Corvol J.-C., Chartier-Harlin M.-C., Mutez E., Brockmann K., Deutschländer A.B., Hadjigeorgiou G.M., Dardiotis E., Stefanis L., Simitsi A.M., Valente E.M., Petrucci S., Duga S., Straniero L., Zecchinelli A., Pezzoli G., Brighina L., Ferrarese C., Annesi G., Quattrone A., Gagliardi M., Matsuo H., Kawamura Y., Hattori N., Nishioka K., Chung S.J., Kim Y.J., Kolber P., van de Warrenburg B.P.C., Bloem B.R., Aasly J., Toft M., Pihlstrøm L., Correia Guedes L., Ferreira J.J., Bardien S., Carr J., Tolosa E., Ezquerra M., Pastor P., Diez-Fairen M., Wirdefeldt K., Pedersen N.L., Ran C., Belin A.C., Puschmann A., Hellberg C., Clarke C.E., Morrison K.E., Tan M., Krainc D., Burbulla L.F., Farrer M.J., Krüger R., Gasser T., Sharma M., Elbaz A., and the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) Consortium

المصدر: Movement Disorders ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128406510&doi=10.1002%2fmds.28902&partnerID=40&md5=1c6beb821e203be47bb0216393c0532fTest

مصطلحات موضوعية: lactase, low density lipoprotein, aged, allele, Article, cholesterol blood level, controlled study, dairy product, disease association, disease duration, female, food intake, genetic association, genetic predisposition, genetic susceptibility, genotype, human, major clinical study, male, Mendelian randomization analysis, obesity, Parkinson disease, randomized controlled trial, risk assessment, sex difference, single nucleotide polymorphism, John Wiley and Sons Inc

الوصف: Background: Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective: The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). Methods: We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results: Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P-difference with women = 0.029). Conclusions: Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society. © 2022 International Parkinson and Movement Disorder Society.

العلاقة: http://hdl.handle.net/11615/73410Test

الإتاحة: https://doi.org/10.1002/mds.28902Test
http://hdl.handle.net/11615/73410Test

المؤلفون: Grover S., Sreelatha A.A.K., Pihlstrom L., Domenighetti C., Schulte C., Sugier P.-E., Radivojkov-Blagojevic M., Lichtner P., Mohamed O., Portugal B., Landoulsi Z., May P., Bobbili D., Edsall C., Bartusch F., Hanussek M., Krüger J., Hernandez D.G., Blauwendraat C., Mellick G.D., Zimprich A., Pirker W., Tan M., Rogaeva E., Lang A., Koks S., Taba P., Lesage S., Brice A., Corvol J.-C., Chartier-Harlin M.-C., Mutez E., Brockmann K., Deutschländer A.B., Hadjigeorgiou G.M., Dardiotis E., Stefanis L., Simitsi A.M., Valente E.M., Petrucci S., Straniero L., Zecchinelli A., Pezzoli G., Brighina L., Ferrarese C., Annesi G., Quattrone A., Gagliardi M., Burbulla L.F., Matsuo H., Kawamura Y., Hattori N., Nishioka K., Chung S.J., Kim Y.J., Pavelka L., Van De Warrenburg B.P.C., Bloem B.R., Singleton A.B., Aasly J., Toft M., Guedes L.C., Ferreira J.J., Bardien S., Carr J., Tolosa E., Ezquerra M., Pastor P., Diez-Fairen M., Wirdefeldt K., Pedersen N.L., Ran C., Belin A.C., Puschmann A., Hellberg C., Clarke C.E., Morrison K.E., Krainc D., Farrer M.J., Kruger R., Elbaz A., Gasser T., Sharma M.

المصدر: Neurology ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85136019610&doi=10.1212%2fWNL.0000000000200699&partnerID=40&md5=7766b3a0615ef70c6f2a5cd8fcdabd2aTest

مصطلحات موضوعية: ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1, adult, Article, BST1 gene, caudate nucleus, CD38 gene, chromosome 12, chromosome 4, chromosome 7, chromosome 8, controlled study, correlation analysis, expression quantitative trait locus, female, gene, gene expression, gene frequency, gene identification, gene linkage disequilibrium, genetic association, genome-wide association study, genotype, genotype phenotype correlation, heritability, human, human tissue, KNH3 gene, major clinical study, male, neuropathology

الوصف: Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10-8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10-9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = -0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10-8). Discussion ...

العلاقة: http://hdl.handle.net/11615/73726Test

الإتاحة: https://doi.org/10.1212/WNL.0000000000200699Test
http://hdl.handle.net/11615/73726Test

المؤلفون: Domenighetti C., Douillard V., Sugier P.-E., Sreelatha A.A.K., Schulte C., Grover S., May P., Bobbili D.R., Radivojkov-Blagojevic M., Lichtner P., Singleton A.B., Hernandez D.G., Edsall C., Gourraud P.-A., Mellick G.D., Zimprich A., Pirker W., Rogaeva E., Lang A.E., Koks S., Taba P., Lesage S., Brice A., Corvol J.-C., Chartier-Harlin M.-C., Mutez E., Brockmann K., Deutschländer A.B., Hadjigeorgiou G.M., Dardiotis E., Stefanis L., Simitsi A.M., Valente E.M., Petrucci S., Duga S., Straniero L., Zecchinelli A., Pezzoli G., Brighina L., Ferrarese C., Annesi G., Quattrone A., Gagliardi M., Matsuo H., Nakayama A., Hattori N., Nishioka K., Chung S.J., Kim Y.J., Kolber P., van de Warrenburg B.P.C., Bloem B.R., Aasly J., Toft M., Pihlstrøm L., Correia Guedes L., Ferreira J.J., Bardien S., Carr J., Tolosa E., Ezquerra M., Pastor P., Diez-Fairen M., Wirdefeldt K., Pedersen N.L., Ran C., Belin A.C., Puschmann A., Ygland Rödström E., Clarke C.E., Morrison K.E., Tan M., KraincMD D., Burbulla L.F., Farrer M.J., Krüger R., Gasser T., Sharma M., Vince N., Elbaz A., Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) Consortium

المصدر: Movement Disorders ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85133891525&doi=10.1002%2fmds.29133&partnerID=40&md5=657ff63a76e864f8b7b498d3e529adf4Test

مصطلحات موضوعية: John Wiley and Sons Inc

الوصف: Background: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions. Objective: To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction. Methods: We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1. Results: At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59–0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern. Conclusions: Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

العلاقة: http://hdl.handle.net/11615/73409Test

الإتاحة: https://doi.org/10.1002/mds.29133Test
http://hdl.handle.net/11615/73409Test

المؤلفون: Grover, S., Kumar Sreelatha, A.A., Pihlstrom, L., Domenighetti, C., Schulte, C., Sugier, P-E, Radivojkov-Blagojevic, M., Lichtner, P., Mohamed, O., Portugal, B., Landoulsi, Z., May, P., Bobbili, D., Edsall, C., Bartusch, F., Hanussek, M., Krüger, J., Hernandez, D.G., Blauwendraat, C., Mellick, G.D., Zimprich, A., Pirker, W., Tan, M., Rogaeva, E., Lang, A., Kõks, S., Taba, P., Lesage, S., Brice, A., Corvol, J-C, Chartier-Harlin, M-C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Burbulla, L.F., Matsuo, H., Kawamura, Y., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y.J., Pavelka, L., van de Warrenburg, B.P.C., Bloem, B.R., Singleton, A.B., Aasly, J., Toft, M., Guedes, L.C., Ferreira, J.J., Bardien, S., Carr, J., Tolosa, E., Ezquerra, M., Pastor, P., Diez-Fairen, M., Wirdefeldt, K., Pedersen, N.L., Ran, C., Belin, A.C., Puschmann, A., Hellberg, C., Clarke, C.E., Morrison, K.E., Krainc, D., Farrer, M.J., Krüger, R., Elbaz, A., Gasser, T., Sharma, M.

المصدر: Grover, S., Kumar Sreelatha, A.A., Pihlstrom, L., Domenighetti, C., Schulte, C., Sugier, P-E, Radivojkov-Blagojevic, M., Lichtner, P., Mohamed, O., Portugal, B., Landoulsi, Z., May, P., Bobbili, D., Edsall, C., Bartusch, F., Hanussek, M., Krüger, J., Hernandez, D.G., Blauwendraat, C., Mellick, G.D., Zimprich, A., Pirker, W., Tan, M., Rogaeva, E., Lang, A., Kõks, S. , Taba, P., Lesage, S., Brice, A., Corvol, J-C, Chartier-Harlin, M-C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Burbulla, ....

الوصف: Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8). Discussion ...

العلاقة: https://researchrepository.murdoch.edu.au/id/eprint/65901Test/; full_text_status:public

الإتاحة: https://researchrepository.murdoch.edu.au/id/eprint/65901Test/

المؤلفون: Domenighetti, C., Douillard, V., Sugier, P‐E, Sreelatha, A.A.K., Schulte, C., Grover, S., May, P., Bobbili, D.R., Radivojkov‐Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Gourraud, P‐A, Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Kõks, S., Taba, P., Lesage, S., Brice, A., Corvol, J‐C, Chartier‐Harlin, M‐C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Duga, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Nakayama, A., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y.J., Kolber, P., van de Warrenburg, B.P.C., Bloem, B.R., Aasly, J., Toft, M., Pihlstrøm, L., Correia Guedes, L., Ferreira, J.J., Bardien, S., Carr, J., Tolosa, E., Ezquerra, M., Pastor, P., Diez‐Fairen, M., Wirdefeldt, K., Pedersen, N.L., Ran, C., Belin, A.C., Puschmann, A., Ygland Rödström, E., Clarke, C.E., Morrison, K.E., Tan, M., KraincMD, D., Burbulla, L.F., Farrer, M.J., Krüger, R., Gasser, T., Sharma, M., Vince, N., Elbaz, A.

المصدر: Domenighetti, C., Douillard, V., Sugier, P‐E, Sreelatha, A.A.K., Schulte, C., Grover, S., May, P., Bobbili, D.R., Radivojkov‐Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Gourraud, P‐A, Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Kõks, S. , Taba, P., Lesage, S., Brice, A., Corvol, J‐C, Chartier‐Harlin, M‐C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Duga, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Nakayama, A., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y.J., ....

الوصف: Background Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions. Objective To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction. Methods We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1. Results At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59–0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern. Conclusions Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association.

العلاقة: https://researchrepository.murdoch.edu.au/id/eprint/65476Test/; full_text_status:public

الإتاحة: https://researchrepository.murdoch.edu.au/id/eprint/65476Test/

المؤلفون: Domenighetti, C., Sugier, P-E, Sreelatha, A.A.K., Schulte, C., Grover, S., Mohamed, O., Portugal, B., May, P., Bobbili, D.R., Radivojkov-Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Kõks, S., Taba, P., Lesage, S., Brice, A., Corvol, J-C, Chartier-Harlin, M-C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Duga, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Kawamura, Y., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y.J., Kolber, P., van de Warrenburg, B.P.C., Bloem, B.R., Aasly, J., Toft, M., Pihlstrøm, L., Guedes, L.C., Ferreira, J.J., Bardien, S., Carr, J., Tolosa, E., Ezquerra, M., Pastor, P., Diez-Fairen, M., Wirdefeldt, K., Pedersen, N.L., Ran, C., Belin, A.C., Puschmann, A., Hellberg, C., Clarke, C.E., Morrison, K.E., Tan, M., Krainc, D., Burbulla, L.F., Farrer, M.J., Krüger, R., Gasser, T., Sharma, M., Elbaz, A.

المصدر: Domenighetti, C., Sugier, P-E, Sreelatha, A.A.K., Schulte, C., Grover, S., Mohamed, O., Portugal, B., May, P., Bobbili, D.R., Radivojkov-Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Kõks, S. , Taba, P., Lesage, S., Brice, A., Corvol, J-C, Chartier-Harlin, M-C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Duga, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Kawamura, Y., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y.J., ....

الوصف: Background:Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective:To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods:We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results:We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion:Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

العلاقة: https://researchrepository.murdoch.edu.au/id/eprint/63804Test/; full_text_status:none

الإتاحة: https://researchrepository.murdoch.edu.au/id/eprint/63804Test/

المؤلفون: Domenighetti, C., Sugier, P‐E, Ashok Kumar Sreelatha, A., Schulte, C., Grover, S., Mohamed, O., Portugal, B., May, P., Bobbili, D.R., Radivojkov‐Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Kõks, S., Taba, P., Lesage, S., Brice, A., Corvol, J‐C, Chartier‐Harlin, M‐C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Duga, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Kawamura, Y., Hattori, N., Nishioka, K., Chung, S.J., Kim, Y.J., Kolber, P., Warrenburg, B.P.C., Bloem, B.R., Aasly, J., Toft, M., Pihlstrøm, L., Correia Guedes, L., Ferreira, J.J., Bardien, S., Carr, J., Tolosa, E., Ezquerra, M., Pastor, P., Diez‐Fairen, M., Wirdefeldt, K., Pedersen, N.L., Ran, C., Belin, A.C., Puschmann, A., Hellberg, C., Clarke, C.E., Morrison, K.E., Tan, M., Krainc, D., Burbulla, L.F., Farrer, M.J., Krüger, R., Gasser, T., Sharma, M., Elbaz, A.

المصدر: Domenighetti, C., Sugier, P‐E, Ashok Kumar Sreelatha, A., Schulte, C., Grover, S., Mohamed, O., Portugal, B., May, P., Bobbili, D.R., Radivojkov‐Blagojevic, M., Lichtner, P., Singleton, A.B., Hernandez, D.G., Edsall, C., Mellick, G.D., Zimprich, A., Pirker, W., Rogaeva, E., Lang, A.E., Kõks, S. , Taba, P., Lesage, S., Brice, A., Corvol, J‐C, Chartier‐Harlin, M‐C, Mutez, E., Brockmann, K., Deutschländer, A.B., Hadjigeorgiou, G.M., Dardiotis, E., Stefanis, L., Simitsi, A.M., Valente, E.M., Petrucci, S., Duga, S., Straniero, L., Zecchinelli, A., Pezzoli, G., Brighina, L., Ferrarese, C., Annesi, G., Quattrone, A., Gagliardi, M., Matsuo, H., Kawamura, Y., Hattori, N., Nishioka, K., Chung, S.J., ....

الوصف: Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). Methods We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P-difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society

العلاقة: https://researchrepository.murdoch.edu.au/id/eprint/63689Test/; full_text_status:none

الإتاحة: https://researchrepository.murdoch.edu.au/id/eprint/63689Test/

المؤلفون: Domenighetti, C. Sugier, P.-E. Sreelatha, A.A.K. Schulte, C. Grover, S. Mohamed, O. Portugal, B. May, P. Bobbili, D.R. Radivojkov-Blagojevic, M. Lichtner, P. Singleton, A.B. Hernandez, D.G. Edsall, C. Mellick, G.D. Zimprich, A. Pirker, W. Rogaeva, E. Lang, A.E. Koks, S. Taba, P. Lesage, S. Brice, A. Corvol, J.-C. Chartier-Harlin, M.-C. Mutez, E. Brockmann, K. Deutschländer, A.B. Hadjigeorgiou, G.M. Dardiotis, E. Stefanis, L. Simitsi, A.M. Valente, E.M. Petrucci, S. Duga, S. Straniero, L. Zecchinelli, A. Pezzoli, G. Brighina, L. Ferrarese, C. Annesi, G. Quattrone, A. Gagliardi, M. Matsuo, H. Kawamura, Y. Hattori, N. Nishioka, K. Chung, S.J. Kim, Y.J. Kolber, P. Van De Warrenburg, B.P.C. Bloem, B.R. Aasly, J. Toft, M. Pihlstrøm, L. Guedes, L.C. Ferreira, J.J. Bardien, S. Carr, J. Tolosa, E. Ezquerra, M. Pastor, P. Diez-Fairen, M. Wirdefeldt, K. Pedersen, N.L. Ran, C. Belin, A.C. Puschmann, A. Hellberg, C. Clarke, C.E. Morrison, K.E. Tan, M. Krainc, D. Burbulla, L.F. Farrer, M.J. Krüger, R. Gasser, T. Sharma, M. Elbaz, A.

الوصف: Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants =67 years old and cases with disease duration =7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power. © 2022 - IOS Press. All rights reserved.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od______2127::af20e886c45cca7b5ebd6f596ed4b55eTest
https://pergamos.lib.uoa.gr/uoa/dl/object/uoadl:2996928Test

المؤلفون: Burbulla, L.F., Schelling, C., Kato, H., Rapaport, D., Woitalla, D., Schiesling, C., Schulte, C., Sharma, M., Illig, T., Bauer, P., Jung, S., Nordheim, A., Schöls, L., Riess, O., Kruger, R.

المصدر: Hum. Mol. Genet. 19, 4437-4452 (2010)

مصطلحات موضوعية: EARLY-ONSET PARKINSONISM, OXIDATIVE STRESS, LINKAGE ANALYSIS, PROTEIN, DJ-1, GENE, MUTATIONS, IMPORT, HSP70, IDENTIFICATION

الوصف: The mitochondrial chaperone mortalin has been linked to neurodegeneration in Parkinson's disease (PD) based on reduced protein levels in affected brain regions of PD patients and its interaction with the PD-associated protein DJ-1. Recently, two amino acid exchanges in the ATPase domain (R126W) and the substrate-binding domain (P509S) of mortalin were identified in Spanish PD patients. Here, we identified a separate and novel variant (A476T) in the substrate-binding domain of mortalin in German PD patients. To define a potential role as a susceptibility factor in PD, we characterized the functions of all three variants in different cellular models. In vitro import assays revealed normal targeting of all mortalin variants. In neuronal and non-neuronal human cell lines, the disease-associated variants caused a mitochondrial phenotype of increased reactive oxygen species and reduced mitochondrial membrane potential, which were exacerbated upon proteolytic stress. These functional impairments correspond with characteristic alterations of the mitochondrial network in cells overexpressing mutant mortalin compared with wild-type (wt), which were confirmed in fibroblasts from a carrier of the A476T variant. In line with a loss of function hypothesis, knockdown of mortalin in human cells caused impaired mitochondrial function that was rescued by wt mortalin, but not by the variants. Our genetic and functional studies of novel disease-associated variants in the mortalin gene define a loss of mortalin function, which causes impaired mitochondrial function and dynamics. Our results support the role of this mitochondrial chaperone in neurodegeneration and underscore the concept of impaired mitochondrial protein quality control in PD.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/20817635; info:eu-repo/semantics/altIdentifier/wos/WOS:000283673500013; info:eu-repo/semantics/altIdentifier/isbn/0964-6906; info:eu-repo/semantics/altIden; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=6091Test; urn:isbn:0964-6906; urn:issn:0964-6906; urn:issn:1460-2083

الإتاحة: https://doi.org/10.1093/hmg/ddq370Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=6091Test