Large-scale replication and heterogeneity in Parkinson disease genetic loci

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Fältnamn	Indikatorer	Metadata
000		06539naa a2201165 4500
001		oai:lup.lub.lu.se:29175224-3e2e-4dd3-a666-43c8f0174d63
003		SwePub
008		170704s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:125101374
024	7	a https://lup.lub.lu.se/record/29175224-3e2e-4dd3-a666-43c8f0174d632 URI
024	7	a https://doi.org/10.1212/WNL.0b013e318264e3532 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1251013742 URI
040		a (SwePub)lud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Sharma, Manuu University of Tübingen4 aut
245	1 0	a Large-scale replication and heterogeneity in Parkinson disease genetic loci
264	1	c 2012
300		a 9 s.
520		a OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.RESULTS: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.CONCLUSION: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
653		a Aged
653		a Alleles
653		a Case-Control Studies
653		a Female
653		a Gene Frequency
653		a Genetic Loci
653		a Genetic Predisposition to Disease
653		a Genome-Wide Association Study
653		a Genotype
653		a Humans
653		a Male
653		a Middle Aged
653		a Parkinson Disease
653		a Polymorphism, Single Nucleotide
653		a Journal Article
700	1	a Ioannidis, John P Au German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
700	1	a Aasly, Jan O.u Stanford University4 aut
700	1	a Annesi, Graziau St. Olav’s University Hospital4 aut
700	1	a Brice, Alexisu National Institute for Health and Medical Research, France4 aut
700	1	a Van Broeckhoven, Christineu University of Antwerp4 aut
700	1	a Bertram, Larsu University of Antwerp4 aut
700	1	a Bozi, Mariau National and Kapodistrian University of Athens4 aut
700	1	a Crosiers, Davidu National and Kapodistrian University of Athens4 aut
700	1	a Clarke, Carl Eu Antwerp University Hospital4 aut
700	1	a Facheris, Maurizio4 aut
700	1	a Farrer, Matthew4 aut
700	1	a Garraux, Gaetan4 aut
700	1	a Gispert, Suzana4 aut
700	1	a Auburger, Georg4 aut
700	1	a Vilariño-Güell, Carles4 aut
700	1	a Hadjigeorgiou, Georgios M.4 aut
700	1	a Hicks, Andrew A4 aut
700	1	a Hattori, Nobutaka4 aut
700	1	a Jeon, Beom S.4 aut
700	1	a Lesage, Suzanne4 aut
700	1	a Lill, Christina M.4 aut
700	1	a Lin, Juei-Jueng4 aut
700	1	a Lynch, Timothy4 aut
700	1	a Lichtner, Peter4 aut
700	1	a Lang, Anthony E4 aut
700	1	a Mok, Vincent4 aut
700	1	a Jasinska-Myga, Barbara4 aut
700	1	a Mellick, George D.4 aut
700	1	a Morrison, Karen E.4 aut
700	1	a Opala, Grzegorz4 aut
700	1	a Pramstaller, Peter P4 aut
700	1	a Pichler, Irene4 aut
700	1	a Park, Sung-Sup4 aut
700	1	a Quattrone, Aldo4 aut
700	1	a Rogaeva, Ekaterina4 aut
700	1	a Ross, Owen A.4 aut
700	1	a Stefanis, Leonidas4 aut
700	1	a Stockton, Joanne D4 aut
700	1	a Satake, Wataru4 aut
700	1	a Silburn, Peter A.4 aut
700	1	a Theuns, Jessie4 aut
700	1	a Tan, Eng-King4 aut
700	1	a Toda, Tatsushi4 aut
700	1	a Tomiyama, Hiroyuki4 aut
700	1	a Uitti, Ryan J.4 aut
700	1	a Wirdefeldt, Karinu Karolinska Institutet4 aut
700	1	a Wszolek, Zbigniew K4 aut
700	1	a Xiromerisiou, Georgia4 aut
700	1	a Puschmann, Andreasu Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-aps
700	1	a Yueh, KC4 aut
700	1	a Zhao, Y4 aut
700	1	a Maraganore, D4 aut
700	1	a Kruger, R4 aut
710	2	a University of Tübingenb German Center for Neurodegenerative Diseases (DZNE), Bonn4 org
710	2	a GEO-PD Consortium
773	0	t Neurologyg 79:7, s. 67-659q 79:7<67-659x 1526-632X
856	4	u https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414661/x freey FULLTEXT
856	4	u http://dx.doi.org/10.1212/WNL.0b013e318264e353y FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/29175224-3e2e-4dd3-a666-43c8f0174d63
856	4 8	u https://doi.org/10.1212/WNL.0b013e318264e353
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:125101374

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Av författaren/redakt...: Sharma, Manu; Ioannidis, John ...; Aasly, Jan O.; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, ...; visa fler...; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl E; Facheris, Mauriz ...; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, ...; Hadjigeorgiou, G ...; Hicks, Andrew A; Hattori, Nobutak ...; Jeon, Beom S.; Lesage, Suzanne; Lill, Christina ...; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E; Mok, Vincent; Jasinska-Myga, B ...; Mellick, George ...; Morrison, Karen ...; Opala, Grzegorz; Pramstaller, Pet ...; Pichler, Irene; Park, Sung-Sup; Quattrone, Aldo; Rogaeva, Ekateri ...; Ross, Owen A.; Stefanis, Leonid ...; Stockton, Joanne ...; Satake, Wataru; Silburn, Peter A ...; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyu ...; Uitti, Ryan J.; Wirdefeldt, Kari ...; Wszolek, Zbignie ...; Xiromerisiou, Ge ...; Puschmann, Andre ...; Yueh, KC; Zhao, Y; Maraganore, D; Kruger, R; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

Artiklar i publikationen: Neurology

Av lärosätet: Lunds universitet; Karolinska Institutet

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