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A two-stage meta-analysis identifies several new loci for Parkinson's disease.

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set o... Full description

Journal Title: PLoS genetics June 2011, Vol.7(6), p.e1002142
Main Author: Plagnol, Vincent
Other Authors: Nalls, Michael A
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1002142
Link: http://search.proquest.com/docview/875721532/?pq-origsite=primo
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title: A two-stage meta-analysis identifies several new loci for Parkinson's disease.
format: Article
creator:
  • Plagnol, Vincent
  • Nalls, Michael A
subjects:
  • Brain–Metabolism
  • DNA Methylation–Genetics
  • Gene Expression Profiling–Genetics
  • Gene Expression Regulation–Genetics
  • Genetic Loci–Genetics
  • Genetic Predisposition to Disease–Genetics
  • Genome-Wide Association Study–Genetics
  • Humans–Genetics
  • Parkinson Disease–Genetics
  • Polymorphism, Single Nucleotide–Genetics
  • Risk Assessment–Genetics
ispartof: PLoS genetics, June 2011, Vol.7(6), p.e1002142
description: A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p
language: eng
source:
identifier: E-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1002142
fulltext: fulltext
issn:
  • 15537404
  • 1553-7404
url: Link


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titleA two-stage meta-analysis identifies several new loci for Parkinson's disease.
creatorPlagnol, Vincent ; Nalls, Michael A
contributorBras, Jose M (record owner) ; Hernandez, Dena G ; Sharma, Manu ; Sheerin, Una-Marie ; Saad, Mohamad ; Simón-Sánchez, Javier ; Schulte, Claudia ; Lesage, Suzanne ; Sveinbjörnsdóttir, Sigurlaug ; Amouyel, Philippe ; Arepalli, Sampath ; Band, Gavin ; Barker, Roger A ; Bellinguez, Céline ; Ben-Shlomo
ispartofPLoS genetics, June 2011, Vol.7(6), p.e1002142
identifierE-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1002142
subjectBrain–Metabolism ; DNA Methylation–Genetics ; Gene Expression Profiling–Genetics ; Gene Expression Regulation–Genetics ; Genetic Loci–Genetics ; Genetic Predisposition to Disease–Genetics ; Genome-Wide Association Study–Genetics ; Humans–Genetics ; Parkinson Disease–Genetics ; Polymorphism, Single Nucleotide–Genetics ; Risk Assessment–Genetics
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descriptionA previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5 × 10 −10 , PARK16 /1q32, STX1B /16p11, FGF20 /8p22, STBD1 /4q21, and GPNMB /7p15). Two of these five loci have been suggested by previous association studies ( PARK16 /1q32, FGF20 /8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16 /1q32, GPNMB /7p15, and STX1B /16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci. Author SummaryThis paper describes the largest case-control analysis of Parkinson's disease to date, with a combined sample set of over 12,000 cases and 21,000 controls. After combining our findings with an independent replication dataset of more than 3,000 cases and 29,000 controls, we found five additional PD risk loci in addition to the 11 loci previously identified in earlier consortium efforts. This successful study further demonstrates the power of the GWA scan experimental design to find new loci contributing to disease risk, even in the context of complex disorders like Parkinson's disease. These new findings provide insights into the etiology of PD and will promote a better understanding of its pathogenesis.
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titleA two-stage meta-analysis identifies several new loci for Parkinson's disease.
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9Amouyel, Philippe
10Arepalli, Sampath
11Band, Gavin
12Barker, Roger A
13Bellinguez, Céline
14Ben-Shlomo, Yoav
15Berendse, Henk W
16Berg, Daniela
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20Bloem, Bas
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26Charlesworth, Gavin
27Chen, Honglei
28Chinnery, Patrick F
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32Cooper, J Mark
33Corvol, Jean Christophe
34Counsell, Carl
35Damier, Philippe
36Dartigues, Jean-François
37Deloukas, Panos
38Deuschl, Günther
39Dexter, David T
40van Dijk, Karin D
41Dillman, Allissa
42Durif, Frank
43Dürr, Alexandra
44Edkins, Sarah
45Evans, Jonathan R
46Foltynie, Thomas
47Freeman, Colin
48Gao, Jianjun
49Gardner, Michelle
50Gibbs, J Raphael
51Goate, Alison
52Gray, Emma
53Guerreiro, Rita
54Gústafsson, Ómar
55Harris, Clare
56Hellenthal, Garrett
57van Hilten, Jacobus J
58Hofman, Albert
59Hollenbeck, Albert
60Holton, Janice
61Hu, Michele
62Huang, Xuemei
63Huber, Heiko
64Hudson, Gavin
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66Huttenlocher, Johanna
67Illig, Thomas
68Jónsson, Pálmi V
69Langford, Cordelia
70Lees, Andrew
71Lichtner, Peter
72Limousin, Patricia
73Lopez, Grisel
74Lorenz, Delia
75Mcneill, Alisdair
76Moorby, Catriona
77Moore, Matthew
78Morris, Huw
79Morrison, Karen E
80Mudanohwo, Ese
81O'Sullivan, Sean S
82Pearson, Justin
83Pearson, Richard
84Perlmutter, Joel S
85Pétursson, Hjörvar
86Pirinen, Matti
87Pollak, Pierre
88Post, Bart
89Potter, Simon
90Ravina, Bernard
91Revesz, Tamas
92Riess, Olaf
93Rivadeneira, Fernando
94Rizzu, Patrizia
95Ryten, Mina
96Sawcer, Stephen
97Schapira, Anthony
98Scheffer, Hans
99Shaw, Karen
100...
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2Bras, Jose M
3Hernandez, Dena G
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7Simón-Sánchez, Javier
8Schulte, Claudia
9Lesage, Suzanne
10Sveinbjörnsdóttir, Sigurlaug
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12Arepalli, Sampath
13Band, Gavin
14Barker, Roger A
15Bellinguez, Céline
16Ben-Shlomo, Yoav
17Berendse, Henk W
18Berg, Daniela
19Bhatia, Kailash
20de Bie, Rob M A
21Biffi, Alessandro
22Bloem, Bas
23Bochdanovits, Zoltan
24Bonin, Michael
25Brockmann, Kathrin
26Brooks, Janet
27Burn, David J
28Charlesworth, Gavin
29Chen, Honglei
30Chinnery, Patrick F
31Chong, Sean
32Clarke, Carl E
33Cookson, Mark R
34Cooper, J Mark
35Corvol, Jean Christophe
36Counsell, Carl
37Damier, Philippe
38Dartigues, Jean-François
39Deloukas, Panos
40Deuschl, Günther
41Dexter, David T
42van Dijk, Karin D
43Dillman, Allissa
44Durif, Frank
45Dürr, Alexandra
46Edkins, Sarah
47Evans, Jonathan R
48Foltynie, Thomas
49Freeman, Colin
50Gao, Jianjun
51Gardner, Michelle
52Gibbs, J Raphael
53Goate, Alison
54Gray, Emma
55Guerreiro, Rita
56Gústafsson, Ómar
57Harris, Clare
58Hellenthal, Garrett
59van Hilten, Jacobus J
60Hofman, Albert
61Hollenbeck, Albert
62Holton, Janice
63Hu, Michele
64Huang, Xuemei
65Huber, Heiko
66Hudson, Gavin
67Hunt, Sarah E
68Huttenlocher, Johanna
69Illig, Thomas
70Jónsson, Pálmi V
71Langford, Cordelia
72Lees, Andrew
73Lichtner, Peter
74Limousin, Patricia
75Lopez, Grisel
76Lorenz, Delia
77Mcneill, Alisdair
78Moorby, Catriona
79Moore, Matthew
80Morris, Huw
81Morrison, Karen E
82Mudanohwo, Ese
83O'Sullivan, Sean S
84Pearson, Justin
85Pearson, Richard
86Perlmutter, Joel S
87Pétursson, Hjörvar
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89Pollak, Pierre
90Post, Bart
91Potter, Simon
92Ravina, Bernard
93Revesz, Tamas
94Riess, Olaf
95Rivadeneira, Fernando
96Rizzu, Patrizia
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7Lesage, Suzanne
8Sveinbjörnsdóttir, Sigurlaug
9Amouyel, Philippe
10Arepalli, Sampath
11Band, Gavin
12Barker, Roger A
13Bellinguez, Céline
14Ben-Shlomo, Yoav
15Berendse, Henk W
16Berg, Daniela
17Bhatia, Kailash
18de Bie, Rob M A
19Biffi, Alessandro
20Bloem, Bas
21Bochdanovits, Zoltan
22Bonin, Michael
23Brockmann, Kathrin
24Brooks, Janet
25Burn, David J
26Charlesworth, Gavin
27Chen, Honglei
28Chinnery, Patrick F
29Chong, Sean
30Clarke, Carl E
31Cookson, Mark R
32Cooper, J Mark
33Corvol, Jean Christophe
34Counsell, Carl
35Damier, Philippe
36Dartigues, Jean-François
37Deloukas, Panos
38Deuschl, Günther
39Dexter, David T
40van Dijk, Karin D
41Dillman, Allissa
42Durif, Frank
43Dürr, Alexandra
44Edkins, Sarah
45Evans, Jonathan R
46Foltynie, Thomas
47Freeman, Colin
48Gao, Jianjun
49Gardner, Michelle
50Gibbs, J Raphael
51Goate, Alison
52Gray, Emma
53Guerreiro, Rita
54Gústafsson, Ómar
55Harris, Clare
56Hellenthal, Garrett
57van Hilten, Jacobus J
58Hofman, Albert
59Hollenbeck, Albert
60Holton, Janice
61Hu, Michele
62Huang, Xuemei
63Huber, Heiko
64Hudson, Gavin
65Hunt, Sarah E
66Huttenlocher, Johanna
67Illig, Thomas
68Jónsson, Pálmi V
69Langford, Cordelia
70Lees, Andrew
71Lichtner, Peter
72Limousin, Patricia
73Lopez, Grisel
74Lorenz, Delia
75McNeill, Alisdair
76Moorby, Catriona
77Moore, Matthew
78Morris, Huw
79Morrison, Karen E
80Mudanohwo, Ese
81O'Sullivan, Sean S
82Pearson, Justin
83Pearson, Richard
84Perlmutter, Joel S
85Pétursson, Hjörvar
86Pirinen, Matti
87Pollak, Pierre
88Post, Bart
89Potter, Simon
90Ravina, Bernard
91Revesz, Tamas
92Riess, Olaf
93Rivadeneira, Fernando
94Rizzu, Patrizia
95Ryten, Mina
96Sawcer, Stephen
97Schapira, Anthony
98Scheffer, Hans
99Shaw, Karen
100...
atitleA two-stage meta-analysis identifies several new loci for Parkinson's disease.
jtitlePLoS genetics
risdate20110601
volume7
issue6
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doi10.1371/journal.pgen.1002142
urlhttp://search.proquest.com/docview/875721532/
issn15537390
date2011-06-01