Large-scale replication and heterogeneity in Parkinson disease genetic loci

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. Investigators...

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Veröffentlicht in:	Neurology 2012-08, Vol.79 (7), p.659-667
Hauptverfasser:	SHARMA, Manu, IOANNIDIS, John P. A, FACHERIS, Maurizio, FARRER, Matthew, GARRAUX, Gaetan, GISPERT, Suzana, AUBURGER, Georg, VILARINO-GÜELL, Carles, HADJIGEORGIOU, Georgios M, HICKS, Andrew A, HATTORI, Nobutaka, JEON, Beom, AASLY, Jan O, LESAGE, Suzanne, LILL, Christina M, LIN, Juei-Jueng, LYNCH, Timothy, LICHTNER, Peter, LANG, Anthony E, MOK, Vincent, JASINSKA-MYGA, Barbara, MELLICK, George D, MORRISON, Karen E, ANNESI, Grazia, OPALA, Grzegorz, PRAMSTALLER, Peter P, PICHLER, Irene, SUNG SUP PARK, QUATTRONE, Aldo, ROGAEVA, Ekaterina, ROSS, Owen A, STEFANIS, Leonidas, STOCKTON, Joanne D, SATAKE, Wataru, BRICE, Alexis, SILBURN, Peter A, THEUNS, Jessie, TAN, Eng-King Tan, TODA, Tatsushi, TOMIYAMA, Hiroyuki, UITTI, Ryan J, WIRDEFELDT, Karin, WSZOLEK, Zbigniew, XIROMERISIOU, Georgia, YUEH, Kuo-Chu, VAN BROECKHOVEN, Christine, YI ZHAO, GASSER, Thomas, MARAGANORE, Demetrius, KRÜGER, Rejko, BERTRAM, Lars, BOZI, Maria, CROSIERS, David, CLARKE, Carl
Format:	Artikel
Sprache:	eng
Schlagworte:	Aged Alleles Basic Medicine Biological and medical sciences Case-Control Studies Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female Gene Frequency genetic Genetic Loci Genetic Predisposition to Disease Genetics & genetic processes Genome-Wide Association Study Genotype Génétique & processus génétiques Human health sciences Humans Life sciences Male Medical and Health Sciences Medical Genetics Medical sciences Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Middle Aged Neurologie Neurology parkinson Parkinson Disease Parkinson Disease - genetics phenotype Polymorphism, Single Nucleotide Sciences de la santé humaine Sciences du vivant trisomy
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container_end_page	667
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container_title	Neurology
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creator	SHARMA, Manu IOANNIDIS, John P. A FACHERIS, Maurizio FARRER, Matthew GARRAUX, Gaetan GISPERT, Suzana AUBURGER, Georg VILARINO-GÜELL, Carles HADJIGEORGIOU, Georgios M HICKS, Andrew A HATTORI, Nobutaka JEON, Beom AASLY, Jan O LESAGE, Suzanne LILL, Christina M LIN, Juei-Jueng LYNCH, Timothy LICHTNER, Peter LANG, Anthony E MOK, Vincent JASINSKA-MYGA, Barbara MELLICK, George D MORRISON, Karen E ANNESI, Grazia OPALA, Grzegorz PRAMSTALLER, Peter P PICHLER, Irene SUNG SUP PARK QUATTRONE, Aldo ROGAEVA, Ekaterina ROSS, Owen A STEFANIS, Leonidas STOCKTON, Joanne D SATAKE, Wataru BRICE, Alexis SILBURN, Peter A THEUNS, Jessie TAN, Eng-King Tan TODA, Tatsushi TOMIYAMA, Hiroyuki UITTI, Ryan J WIRDEFELDT, Karin WSZOLEK, Zbigniew XIROMERISIOU, Georgia YUEH, Kuo-Chu VAN BROECKHOVEN, Christine YI ZHAO GASSER, Thomas MARAGANORE, Demetrius KRÜGER, Rejko BERTRAM, Lars BOZI, Maria CROSIERS, David CLARKE, Carl
description	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. 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. 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. 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.
doi_str_mv	10.1212/wnl.0b013e318264e353
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A ; FACHERIS, Maurizio ; FARRER, Matthew ; GARRAUX, Gaetan ; GISPERT, Suzana ; AUBURGER, Georg ; VILARINO-GÜELL, Carles ; HADJIGEORGIOU, Georgios M ; HICKS, Andrew A ; HATTORI, Nobutaka ; JEON, Beom ; AASLY, Jan O ; LESAGE, Suzanne ; LILL, Christina M ; LIN, Juei-Jueng ; LYNCH, Timothy ; LICHTNER, Peter ; LANG, Anthony E ; MOK, Vincent ; JASINSKA-MYGA, Barbara ; MELLICK, George D ; MORRISON, Karen E ; ANNESI, Grazia ; OPALA, Grzegorz ; PRAMSTALLER, Peter P ; PICHLER, Irene ; SUNG SUP PARK ; QUATTRONE, Aldo ; ROGAEVA, Ekaterina ; ROSS, Owen A ; STEFANIS, Leonidas ; STOCKTON, Joanne D ; SATAKE, Wataru ; BRICE, Alexis ; SILBURN, Peter A ; THEUNS, Jessie ; TAN, Eng-King Tan ; TODA, Tatsushi ; TOMIYAMA, Hiroyuki ; UITTI, Ryan J ; WIRDEFELDT, Karin ; WSZOLEK, Zbigniew ; XIROMERISIOU, Georgia ; YUEH, Kuo-Chu ; VAN BROECKHOVEN, Christine ; YI ZHAO ; GASSER, Thomas ; MARAGANORE, Demetrius ; KRÜGER, Rejko ; BERTRAM, Lars ; BOZI, Maria ; CROSIERS, David ; CLARKE, Carl</creator><creatorcontrib>SHARMA, Manu ; IOANNIDIS, John P. A ; FACHERIS, Maurizio ; FARRER, Matthew ; GARRAUX, Gaetan ; GISPERT, Suzana ; AUBURGER, Georg ; VILARINO-GÜELL, Carles ; HADJIGEORGIOU, Georgios M ; HICKS, Andrew A ; HATTORI, Nobutaka ; JEON, Beom ; AASLY, Jan O ; LESAGE, Suzanne ; LILL, Christina M ; LIN, Juei-Jueng ; LYNCH, Timothy ; LICHTNER, Peter ; LANG, Anthony E ; MOK, Vincent ; JASINSKA-MYGA, Barbara ; MELLICK, George D ; MORRISON, Karen E ; ANNESI, Grazia ; OPALA, Grzegorz ; PRAMSTALLER, Peter P ; PICHLER, Irene ; SUNG SUP PARK ; QUATTRONE, Aldo ; ROGAEVA, Ekaterina ; ROSS, Owen A ; STEFANIS, Leonidas ; STOCKTON, Joanne D ; SATAKE, Wataru ; BRICE, Alexis ; SILBURN, Peter A ; THEUNS, Jessie ; TAN, Eng-King Tan ; TODA, Tatsushi ; TOMIYAMA, Hiroyuki ; UITTI, Ryan J ; WIRDEFELDT, Karin ; WSZOLEK, Zbigniew ; XIROMERISIOU, Georgia ; YUEH, Kuo-Chu ; VAN BROECKHOVEN, Christine ; YI ZHAO ; GASSER, Thomas ; MARAGANORE, Demetrius ; KRÜGER, Rejko ; BERTRAM, Lars ; BOZI, Maria ; CROSIERS, David ; CLARKE, Carl ; GEO-PD Consortium</creatorcontrib><description>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. 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. 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. 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.</description><identifier>ISSN: 0028-3878</identifier><identifier>ISSN: 1526-632X</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/wnl.0b013e318264e353</identifier><identifier>PMID: 22786590</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Aged ; Alleles ; Basic Medicine ; Biological and medical sciences ; Case-Control Studies ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Female ; Gene Frequency ; genetic ; Genetic Loci ; Genetic Predisposition to Disease ; Genetics & genetic processes ; Genome-Wide Association Study ; Genotype ; Génétique & processus génétiques ; Human health sciences ; Humans ; Life sciences ; Male ; Medical and Health Sciences ; Medical Genetics ; Medical sciences ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Middle Aged ; Neurologie ; Neurology ; parkinson ; Parkinson Disease ; Parkinson Disease - genetics ; phenotype ; Polymorphism, Single Nucleotide ; Sciences de la santé humaine ; Sciences du vivant ; trisomy</subject><ispartof>Neurology, 2012-08, Vol.79 (7), p.659-667</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 by AAN Enterprises, Inc. 2012 AAN Enterprises, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c688t-7a40dae97303d551df322906b119e0cce0e1dc8fbbab3a7ce3aaffd5391a75d53</citedby><cites>FETCH-LOGICAL-c688t-7a40dae97303d551df322906b119e0cce0e1dc8fbbab3a7ce3aaffd5391a75d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26275387$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22786590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/29175224-3e2e-4dd3-a666-43c8f0174d63$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:125101374$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>SHARMA, Manu</creatorcontrib><creatorcontrib>IOANNIDIS, John P. A</creatorcontrib><creatorcontrib>FACHERIS, Maurizio</creatorcontrib><creatorcontrib>FARRER, Matthew</creatorcontrib><creatorcontrib>GARRAUX, Gaetan</creatorcontrib><creatorcontrib>GISPERT, Suzana</creatorcontrib><creatorcontrib>AUBURGER, Georg</creatorcontrib><creatorcontrib>VILARINO-GÜELL, Carles</creatorcontrib><creatorcontrib>HADJIGEORGIOU, Georgios M</creatorcontrib><creatorcontrib>HICKS, Andrew A</creatorcontrib><creatorcontrib>HATTORI, Nobutaka</creatorcontrib><creatorcontrib>JEON, Beom</creatorcontrib><creatorcontrib>AASLY, Jan O</creatorcontrib><creatorcontrib>LESAGE, Suzanne</creatorcontrib><creatorcontrib>LILL, Christina M</creatorcontrib><creatorcontrib>LIN, Juei-Jueng</creatorcontrib><creatorcontrib>LYNCH, Timothy</creatorcontrib><creatorcontrib>LICHTNER, Peter</creatorcontrib><creatorcontrib>LANG, Anthony E</creatorcontrib><creatorcontrib>MOK, Vincent</creatorcontrib><creatorcontrib>JASINSKA-MYGA, Barbara</creatorcontrib><creatorcontrib>MELLICK, George D</creatorcontrib><creatorcontrib>MORRISON, Karen E</creatorcontrib><creatorcontrib>ANNESI, Grazia</creatorcontrib><creatorcontrib>OPALA, Grzegorz</creatorcontrib><creatorcontrib>PRAMSTALLER, Peter P</creatorcontrib><creatorcontrib>PICHLER, Irene</creatorcontrib><creatorcontrib>SUNG SUP PARK</creatorcontrib><creatorcontrib>QUATTRONE, Aldo</creatorcontrib><creatorcontrib>ROGAEVA, Ekaterina</creatorcontrib><creatorcontrib>ROSS, Owen A</creatorcontrib><creatorcontrib>STEFANIS, Leonidas</creatorcontrib><creatorcontrib>STOCKTON, Joanne D</creatorcontrib><creatorcontrib>SATAKE, Wataru</creatorcontrib><creatorcontrib>BRICE, Alexis</creatorcontrib><creatorcontrib>SILBURN, Peter A</creatorcontrib><creatorcontrib>THEUNS, Jessie</creatorcontrib><creatorcontrib>TAN, Eng-King Tan</creatorcontrib><creatorcontrib>TODA, Tatsushi</creatorcontrib><creatorcontrib>TOMIYAMA, Hiroyuki</creatorcontrib><creatorcontrib>UITTI, Ryan J</creatorcontrib><creatorcontrib>WIRDEFELDT, Karin</creatorcontrib><creatorcontrib>WSZOLEK, Zbigniew</creatorcontrib><creatorcontrib>XIROMERISIOU, Georgia</creatorcontrib><creatorcontrib>YUEH, Kuo-Chu</creatorcontrib><creatorcontrib>VAN BROECKHOVEN, Christine</creatorcontrib><creatorcontrib>YI ZHAO</creatorcontrib><creatorcontrib>GASSER, Thomas</creatorcontrib><creatorcontrib>MARAGANORE, Demetrius</creatorcontrib><creatorcontrib>KRÜGER, Rejko</creatorcontrib><creatorcontrib>BERTRAM, Lars</creatorcontrib><creatorcontrib>BOZI, Maria</creatorcontrib><creatorcontrib>CROSIERS, David</creatorcontrib><creatorcontrib>CLARKE, Carl</creatorcontrib><creatorcontrib>GEO-PD Consortium</creatorcontrib><title>Large-scale replication and heterogeneity in Parkinson disease genetic loci</title><title>Neurology</title><addtitle>Neurology</addtitle><description>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. 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. 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. 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.</description><subject>Aged</subject><subject>Alleles</subject><subject>Basic Medicine</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>genetic</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics & genetic processes</subject><subject>Genome-Wide Association Study</subject><subject>Genotype</subject><subject>Génétique & processus génétiques</subject><subject>Human health sciences</subject><subject>Humans</subject><subject>Life sciences</subject><subject>Male</subject><subject>Medical and Health Sciences</subject><subject>Medical Genetics</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicinsk genetik</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>Middle Aged</subject><subject>Neurologie</subject><subject>Neurology</subject><subject>parkinson</subject><subject>Parkinson Disease</subject><subject>Parkinson Disease - genetics</subject><subject>phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Sciences de la santé humaine</subject><subject>Sciences du vivant</subject><subject>trisomy</subject><issn>0028-3878</issn><issn>1526-632X</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqFUk1v1DAQjRCILoV_gFAuSFxSbI8_4gsSqvgSEXAAwc1y7MnW1JssdrZV_z1OdykUCXGwZuT35vmN9arqMSUnlFH2_HKMJ6QnFBBoyyRHEHCnWlHBZCOBfbtbrQhhbQOtao-qBzl_J6SASt-vjhhTrRSarKr3nU1rbLKzEeuE2xicncM01nb09RnOmKY1jhjmqzqM9SebzsOYC-xDRpuxXsA5uDpOLjys7g02Znx0qMfVl9evPp--bbqPb96dvuwaJ9t2bpTlxFvUCgh4IagfgDFNZE-pRuIcEqTetUPf2x6scgjWDoMXoKlVotTjqtnr5kvc7nqzTWFj05WZbDCHq_PSoREgtOCF3_2TH3fbcvpylgGmqRKMcQPI0HDvwVgppeFQ_BCquJdQ5F7s5YrWBr3DcU423lK9jYzhzKynCwOccilpEYC9QAy4RjOlPpgLdj143e_i2lhn-uKHydZQYEotWzw7PJumHzvMs9mE7DBGO-K0y4YW87J41_B_KuFEaxDt4oXvqS5NOSccbvagxCw5M18_dObvnJWxJ3_-wc3Qr2AVwtMDwS7ZGpIdXci_eZIpUZIJPwHGvN2H</recordid><startdate>20120814</startdate><enddate>20120814</enddate><creator>SHARMA, Manu</creator><creator>IOANNIDIS, John P. 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A ; FACHERIS, Maurizio ; FARRER, Matthew ; GARRAUX, Gaetan ; GISPERT, Suzana ; AUBURGER, Georg ; VILARINO-GÜELL, Carles ; HADJIGEORGIOU, Georgios M ; HICKS, Andrew A ; HATTORI, Nobutaka ; JEON, Beom ; AASLY, Jan O ; LESAGE, Suzanne ; LILL, Christina M ; LIN, Juei-Jueng ; LYNCH, Timothy ; LICHTNER, Peter ; LANG, Anthony E ; MOK, Vincent ; JASINSKA-MYGA, Barbara ; MELLICK, George D ; MORRISON, Karen E ; ANNESI, Grazia ; OPALA, Grzegorz ; PRAMSTALLER, Peter P ; PICHLER, Irene ; SUNG SUP PARK ; QUATTRONE, Aldo ; ROGAEVA, Ekaterina ; ROSS, Owen A ; STEFANIS, Leonidas ; STOCKTON, Joanne D ; SATAKE, Wataru ; BRICE, Alexis ; SILBURN, Peter A ; THEUNS, Jessie ; TAN, Eng-King Tan ; TODA, Tatsushi ; TOMIYAMA, Hiroyuki ; UITTI, Ryan J ; WIRDEFELDT, Karin ; WSZOLEK, Zbigniew ; XIROMERISIOU, Georgia ; YUEH, Kuo-Chu ; VAN BROECKHOVEN, Christine ; YI ZHAO ; GASSER, Thomas ; MARAGANORE, Demetrius ; KRÜGER, Rejko ; BERTRAM, Lars ; BOZI, Maria ; CROSIERS, David ; CLARKE, Carl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c688t-7a40dae97303d551df322906b119e0cce0e1dc8fbbab3a7ce3aaffd5391a75d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Alleles</topic><topic>Basic Medicine</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>genetic</topic><topic>Genetic Loci</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics & genetic processes</topic><topic>Genome-Wide Association Study</topic><topic>Genotype</topic><topic>Génétique & processus génétiques</topic><topic>Human health sciences</topic><topic>Humans</topic><topic>Life sciences</topic><topic>Male</topic><topic>Medical and Health Sciences</topic><topic>Medical Genetics</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicinsk genetik</topic><topic>Medicinska och farmaceutiska grundvetenskaper</topic><topic>Middle Aged</topic><topic>Neurologie</topic><topic>Neurology</topic><topic>parkinson</topic><topic>Parkinson Disease</topic><topic>Parkinson Disease - genetics</topic><topic>phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Sciences de la santé humaine</topic><topic>Sciences du vivant</topic><topic>trisomy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SHARMA, Manu</creatorcontrib><creatorcontrib>IOANNIDIS, John P. A</creatorcontrib><creatorcontrib>FACHERIS, Maurizio</creatorcontrib><creatorcontrib>FARRER, Matthew</creatorcontrib><creatorcontrib>GARRAUX, Gaetan</creatorcontrib><creatorcontrib>GISPERT, Suzana</creatorcontrib><creatorcontrib>AUBURGER, Georg</creatorcontrib><creatorcontrib>VILARINO-GÜELL, Carles</creatorcontrib><creatorcontrib>HADJIGEORGIOU, Georgios M</creatorcontrib><creatorcontrib>HICKS, Andrew A</creatorcontrib><creatorcontrib>HATTORI, Nobutaka</creatorcontrib><creatorcontrib>JEON, Beom</creatorcontrib><creatorcontrib>AASLY, Jan O</creatorcontrib><creatorcontrib>LESAGE, Suzanne</creatorcontrib><creatorcontrib>LILL, Christina M</creatorcontrib><creatorcontrib>LIN, Juei-Jueng</creatorcontrib><creatorcontrib>LYNCH, Timothy</creatorcontrib><creatorcontrib>LICHTNER, Peter</creatorcontrib><creatorcontrib>LANG, Anthony E</creatorcontrib><creatorcontrib>MOK, Vincent</creatorcontrib><creatorcontrib>JASINSKA-MYGA, Barbara</creatorcontrib><creatorcontrib>MELLICK, George D</creatorcontrib><creatorcontrib>MORRISON, Karen E</creatorcontrib><creatorcontrib>ANNESI, Grazia</creatorcontrib><creatorcontrib>OPALA, Grzegorz</creatorcontrib><creatorcontrib>PRAMSTALLER, Peter P</creatorcontrib><creatorcontrib>PICHLER, Irene</creatorcontrib><creatorcontrib>SUNG SUP PARK</creatorcontrib><creatorcontrib>QUATTRONE, Aldo</creatorcontrib><creatorcontrib>ROGAEVA, Ekaterina</creatorcontrib><creatorcontrib>ROSS, Owen A</creatorcontrib><creatorcontrib>STEFANIS, Leonidas</creatorcontrib><creatorcontrib>STOCKTON, Joanne D</creatorcontrib><creatorcontrib>SATAKE, Wataru</creatorcontrib><creatorcontrib>BRICE, Alexis</creatorcontrib><creatorcontrib>SILBURN, Peter A</creatorcontrib><creatorcontrib>THEUNS, Jessie</creatorcontrib><creatorcontrib>TAN, Eng-King Tan</creatorcontrib><creatorcontrib>TODA, Tatsushi</creatorcontrib><creatorcontrib>TOMIYAMA, Hiroyuki</creatorcontrib><creatorcontrib>UITTI, Ryan J</creatorcontrib><creatorcontrib>WIRDEFELDT, Karin</creatorcontrib><creatorcontrib>WSZOLEK, Zbigniew</creatorcontrib><creatorcontrib>XIROMERISIOU, Georgia</creatorcontrib><creatorcontrib>YUEH, Kuo-Chu</creatorcontrib><creatorcontrib>VAN BROECKHOVEN, Christine</creatorcontrib><creatorcontrib>YI ZHAO</creatorcontrib><creatorcontrib>GASSER, Thomas</creatorcontrib><creatorcontrib>MARAGANORE, Demetrius</creatorcontrib><creatorcontrib>KRÜGER, Rejko</creatorcontrib><creatorcontrib>BERTRAM, Lars</creatorcontrib><creatorcontrib>BOZI, Maria</creatorcontrib><creatorcontrib>CROSIERS, David</creatorcontrib><creatorcontrib>CLARKE, Carl</creatorcontrib><creatorcontrib>GEO-PD Consortium</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Université de Liège - Open Repository and Bibliography (ORBI)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SWEPUB Lunds universitet full text</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Lunds universitet</collection><collection>SwePub Articles full text</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SHARMA, Manu</au><au>IOANNIDIS, John P. A</au><au>FACHERIS, Maurizio</au><au>FARRER, Matthew</au><au>GARRAUX, Gaetan</au><au>GISPERT, Suzana</au><au>AUBURGER, Georg</au><au>VILARINO-GÜELL, Carles</au><au>HADJIGEORGIOU, Georgios M</au><au>HICKS, Andrew A</au><au>HATTORI, Nobutaka</au><au>JEON, Beom</au><au>AASLY, Jan O</au><au>LESAGE, Suzanne</au><au>LILL, Christina M</au><au>LIN, Juei-Jueng</au><au>LYNCH, Timothy</au><au>LICHTNER, Peter</au><au>LANG, Anthony E</au><au>MOK, Vincent</au><au>JASINSKA-MYGA, Barbara</au><au>MELLICK, George D</au><au>MORRISON, Karen E</au><au>ANNESI, Grazia</au><au>OPALA, Grzegorz</au><au>PRAMSTALLER, Peter P</au><au>PICHLER, Irene</au><au>SUNG SUP PARK</au><au>QUATTRONE, Aldo</au><au>ROGAEVA, Ekaterina</au><au>ROSS, Owen A</au><au>STEFANIS, Leonidas</au><au>STOCKTON, Joanne D</au><au>SATAKE, Wataru</au><au>BRICE, Alexis</au><au>SILBURN, Peter A</au><au>THEUNS, Jessie</au><au>TAN, Eng-King Tan</au><au>TODA, Tatsushi</au><au>TOMIYAMA, Hiroyuki</au><au>UITTI, Ryan J</au><au>WIRDEFELDT, Karin</au><au>WSZOLEK, Zbigniew</au><au>XIROMERISIOU, Georgia</au><au>YUEH, Kuo-Chu</au><au>VAN BROECKHOVEN, Christine</au><au>YI ZHAO</au><au>GASSER, Thomas</au><au>MARAGANORE, Demetrius</au><au>KRÜGER, Rejko</au><au>BERTRAM, Lars</au><au>BOZI, Maria</au><au>CROSIERS, David</au><au>CLARKE, Carl</au><aucorp>GEO-PD Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Large-scale replication and heterogeneity in Parkinson disease genetic loci</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2012-08-14</date><risdate>2012</risdate><volume>79</volume><issue>7</issue><spage>659</spage><epage>667</epage><pages>659-667</pages><issn>0028-3878</issn><issn>1526-632X</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>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. 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. 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. 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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>22786590</pmid><doi>10.1212/wnl.0b013e318264e353</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects	Aged Alleles Basic Medicine Biological and medical sciences Case-Control Studies Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female Gene Frequency genetic Genetic Loci Genetic Predisposition to Disease Genetics & genetic processes Genome-Wide Association Study Genotype Génétique & processus génétiques Human health sciences Humans Life sciences Male Medical and Health Sciences Medical Genetics Medical sciences Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Middle Aged Neurologie Neurology parkinson Parkinson Disease Parkinson Disease - genetics phenotype Polymorphism, Single Nucleotide Sciences de la santé humaine Sciences du vivant trisomy
title	Large-scale replication and heterogeneity in Parkinson disease genetic loci
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