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Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: the PDgene database
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نویسنده
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lill c.m. ,roehr j.t. ,mcqueen m.b. ,kavvoura f.k. ,bagade s. ,schjeide b.-m.m. ,schjeide l.m. ,meissner e. ,zauft u. ,allen n.c. ,liu t. ,schilling m. ,anderson k.j. ,beecham g. ,berg d. ,biernacka j.m. ,brice a. ,destefano a.l. ,do c.b. ,eriksson n. ,factor s.a. ,farrer m.j. ,foroud t. ,gasser t. ,hamza t. ,hardy j.a. ,heutink p. ,hill-burns e.m. ,klein c. ,latourelle j.c. ,maraganore d.m. ,martin e.r. ,martinez m. ,myers r.h. ,nalls m.a. ,pankratz n. ,payami h. ,satake w. ,scott w.k. ,sharma m. ,singleton a.b. ,stefansson k. ,toda t. ,tung j.y. ,vance j. ,wood n.w. ,zabetian c.p. ,young p. ,tanzi r.e. ,khoury m.j. ,zipp f. ,lehrach h. ,ioannidis j.p.a. ,bertram l.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 3
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چکیده
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More than 800 published genetic association studies have implicated dozens of potential risk loci in parkinson's disease (pd). to facilitate the interpretation of these findings,we have created a dedicated online resource,pdgene,that comprehensively collects and meta-analyzes all published studies in the field. a systematic literature screen of ~27,000 articles yielded 828 eligible articles from which relevant data were extracted. in addition,individual-level data from three publicly available genome-wide association studies (gwas) were obtained and subjected to genotype imputation and analysis. overall,we performed meta-analyses on more than seven million polymorphisms originating either from gwas datasets and/or from smaller scale pd association studies. meta-analyses on 147 snps were supplemented by unpublished gwas data from up to 16,452 pd cases and 48,810 controls. eleven loci showed genome-wide significant (p>5×10-8) association with disease risk: bst1,ccdc62/hip1r,dgkq/gak,gba,lrrk2,mapt,mccc1/lamp3,park16,snca,stk39,and syt11/rab25. in addition,we identified novel evidence for genome-wide significant association with a polymorphism in itga8 (rs7077361,or 0.88,p = 1.3×10-8). all meta-analysis results are freely available on a dedicated online database (www.pdgene.org),which is cross-linked with a customized track on the ucsc genome browser. our study provides an exhaustive and up-to-date summary of the status of pd genetics research that can be readily scaled to include the results of future large-scale genetics projects,including next-generation sequencing studies.
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آدرس
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neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin,germany,department of neurology,massachusetts general hospital,charlestown,ma,united states,department of neurology,medical center of the johannes gutenberg-university,mainz,germany,department of neurology,university hospital,münster, Germany, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin,germany,department of mathematics and computer science,free university,berlin, Germany, institute for behavioral genetics,university of colorado,boulder,co, United States, clinical and molecular epidemiology unit,department of hygiene and epidemiology,university of ioannina school of medicine,ioannina,greece,centre for diabetes and endocrinology,royal berkshire hospital,reading,united kingdom,oxford centre for diabetes,endocrinology,and metabolism,churchill hospital,university of oxford,oxford, United Kingdom, department of neurology,massachusetts general hospital,charlestown,ma, United States, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin, Germany, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin, Germany, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin, Germany, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin, Germany, department of neurology,massachusetts general hospital,charlestown,ma, United States, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin,germany,max planck institute for human development,berlin, Germany, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin,germany,department of mathematics and computer science,free university,berlin, Germany, department of health sciences research,mayo clinic,rochester,mn, United States, john p. hussman institute for human genomics,miller school of medicine,university of miami,miami,fl, United States, department for neurodegenerative diseases,hertie institute for clinical brain research,university of tübingen,tübingen,germany,dzne,german center for neurodegenerative diseases,tübingen, Germany, department of health sciences research,mayo clinic,rochester,mn, United States, inserm,umr-s975,paris,france,université pierre et marie curie-paris,centre de recherche de l'institut du cerveau et de la moelle épinière,umr-s975,paris,france,cnrs,umr 7225,paris,france,ap-hp,pitié-salpêtrière hospital,department of genetics and cytogenetics,paris, France, department of neurology,boston university school of medicine,boston university,boston,ma,united states,department of biostatistics,boston university school of public health,boston,ma, United States, 23andme,mountain view,ca, United States, 23andme,mountain view,ca, United States, department of neurology,emory university school of medicine,atlanta,ga, United States, department of medical genetics,university of british columbia,vancouver, Canada, indiana university school of medicine,indianapolis,in, United States, department for neurodegenerative diseases,hertie institute for clinical brain research,university of tübingen,tübingen,germany,dzne,german center for neurodegenerative diseases,tübingen, Germany, new york state department of health wadsworth center,albany,ny, United States, department of molecular neuroscience,ucl institute of neurology,university college london,london, United Kingdom, department of clinical genetics,section of medical genomics,vu university medical centre,amsterdam, Netherlands, new york state department of health wadsworth center,albany,ny, United States, section of clinical and molecular neurogenetics,department of neurology,university of lübeck,lübeck, Germany, department of neurology,boston university school of medicine,boston university,boston,ma, United States, department of neurology,northshore university health system,evanston,il, United States, john p. hussman institute for human genomics,miller school of medicine,university of miami,miami,fl, United States, inserm umr 1043,cptp,toulouse,france,paul sabatier university,toulouse, France, department of neurology,boston university school of medicine,boston university,boston,ma, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, indiana university school of medicine,indianapolis,in, United States, new york state department of health wadsworth center,albany,ny, United States, division of neurology/molecular brain science,kobe university graduate school of medicine,kobe, Japan, john p. hussman institute for human genomics,miller school of medicine,university of miami,miami,fl, United States, department for neurodegenerative diseases,hertie institute for clinical brain research,university of tübingen,tübingen,germany,dzne,german center for neurodegenerative diseases,tübingen, Germany, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, decode genetics,reykjavik, Iceland, division of neurology/molecular brain science,kobe university graduate school of medicine,kobe, Japan, 23andme,mountain view,ca, United States, john p. hussman institute for human genomics,miller school of medicine,university of miami,miami,fl, United States, department of molecular neuroscience,ucl institute of neurology,university college london,london,united kingdom,ucl genetics institute,university college london,london, United Kingdom, va puget sound health care system and department of neurology,university of washington,seattle,wa, United States, department of neurology,university hospital,münster, Germany, department of neurology,massachusetts general hospital,charlestown,ma, United States, office of public health genomics,centers for disease control and prevention,atlanta,ga, United States, department of neurology,medical center of the johannes gutenberg-university,mainz, Germany, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin, Germany, clinical and molecular epidemiology unit,department of hygiene and epidemiology,university of ioannina school of medicine,ioannina,greece,biomedical research institute,foundation for research and technology-hellas,ioannina,greece,center for genetic epidemiology and modeling and tufts clinical,translational science institute,tufts university school of medicine,boston,ma,united states,stanford prevention research center,department of medicine and department of health research and policy,stanford university school of medicine,stanford,ca, United States, neuropsychiatric genetics group,department of vertebrate genomics,max planck institute for molecular genetics,berlin,germany,department of neurology,massachusetts general hospital,charlestown,ma, United States
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Authors
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