Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study
Identifieur interne : 009826 ( Main/Exploration ); précédent : 009825; suivant : 009827Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study
Auteurs : Alexis Elbaz ; Lorene M. Nelson ; Haydeh Payami ; John P A. Ioannidis ; Brian K. Fiske ; Grazia Annesi ; Andrea Carmine Belin ; Stewart A. Factor ; Carlo Ferrarese ; Georgios M. Hadjigeorgiou ; Donald S. Higgins ; Hideshi Kawakami ; Rejko Krüger ; Karen S. Marder ; Richard P. Mayeux ; George D. Mellick ; John G. Nutt ; Beate Ritz ; Ali Samii ; Caroline M. Tanner ; Christine Van Broeckhoven ; Stephen K. Van Den Eeden ; Karin Wirdefeldt ; Cyrus P. Zabetian ; Marie Dehem ; Jennifer S. Montimurro ; Audrey Southwick ; Richard M. Myers ; Thomas A. TrikalinosSource :
- Lancet neurology [ 1474-4422 ] ; 2006.
Abstract
A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson’s disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain.
Investigators from three Michael J Fox Foundation for Parkinson’s Research-funded genetics consortia—comprising 14 teams—contributed DNA samples from 5526 patients with Parkinson’s disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies.
In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0·89 to 1·09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0·95 to 1.08); there was little heterogeneity except for SNP rs7520966.
Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson’s disease.
Url:
DOI: 10.1016/S1474-4422(06)70579-8
PubMed: 17052658
PubMed Central: 3636768
Affiliations:
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Myers</name></author><author><name sortKey="Trikalinos, Thomas A" sort="Trikalinos, Thomas A" uniqKey="Trikalinos T" first="Thomas A" last="Trikalinos">Thomas A. 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Nelson</name></author><author><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P A" last="Ioannidis">John P A. Ioannidis</name></author><author><name sortKey="Fiske, Brian K" sort="Fiske, Brian K" uniqKey="Fiske B" first="Brian K" last="Fiske">Brian K. Fiske</name></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name></author><author><name sortKey="Belin, Andrea Carmine" sort="Belin, Andrea Carmine" uniqKey="Belin A" first="Andrea Carmine" last="Belin">Andrea Carmine Belin</name></author><author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A" last="Factor">Stewart A. Factor</name></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M" last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name></author><author><name sortKey="Higgins, Donald S" sort="Higgins, Donald S" uniqKey="Higgins D" first="Donald S" last="Higgins">Donald S. Higgins</name></author><author><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name></author><author><name sortKey="Marder, Karen S" sort="Marder, Karen S" uniqKey="Marder K" first="Karen S" last="Marder">Karen S. Marder</name></author><author><name sortKey="Mayeux, Richard P" sort="Mayeux, Richard P" uniqKey="Mayeux R" first="Richard P" last="Mayeux">Richard P. Mayeux</name></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D" last="Mellick">George D. Mellick</name></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G" last="Nutt">John G. Nutt</name></author><author><name sortKey="Ritz, Beate" sort="Ritz, Beate" uniqKey="Ritz B" first="Beate" last="Ritz">Beate Ritz</name></author><author><name sortKey="Samii, Ali" sort="Samii, Ali" uniqKey="Samii A" first="Ali" last="Samii">Ali Samii</name></author><author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M" last="Tanner">Caroline M. Tanner</name></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name></author><author><name sortKey="Van Den Eeden, Stephen K" sort="Van Den Eeden, Stephen K" uniqKey="Van Den Eeden S" first="Stephen K" last="Van Den Eeden">Stephen K. Van Den Eeden</name></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P" last="Zabetian">Cyrus P. Zabetian</name></author><author><name sortKey="Dehem, Marie" sort="Dehem, Marie" uniqKey="Dehem M" first="Marie" last="Dehem">Marie Dehem</name></author><author><name sortKey="Montimurro, Jennifer S" sort="Montimurro, Jennifer S" uniqKey="Montimurro J" first="Jennifer S" last="Montimurro">Jennifer S. Montimurro</name></author><author><name sortKey="Southwick, Audrey" sort="Southwick, Audrey" uniqKey="Southwick A" first="Audrey" last="Southwick">Audrey Southwick</name></author><author><name sortKey="Myers, Richard M" sort="Myers, Richard M" uniqKey="Myers R" first="Richard M" last="Myers">Richard M. Myers</name></author><author><name sortKey="Trikalinos, Thomas A" sort="Trikalinos, Thomas A" uniqKey="Trikalinos T" first="Thomas A" last="Trikalinos">Thomas A. Trikalinos</name></author></analytic><series><title level="j">Lancet neurology</title><idno type="ISSN">1474-4422</idno><idno type="eISSN">1474-4465</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec id="S1"><title>Background</title><p id="P1">A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson’s disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Investigators from three Michael J Fox Foundation for Parkinson’s Research-funded genetics consortia—comprising 14 teams—contributed DNA samples from 5526 patients with Parkinson’s disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies.</p></sec><sec id="S3"><title>Findings</title><p id="P3">In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0·89 to 1·09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0·95 to 1.08); there was little heterogeneity except for SNP rs7520966.</p></sec><sec id="S4"><title>Interpretation</title><p id="P4">Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson’s disease.</p></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><name sortKey="Belin, Andrea Carmine" sort="Belin, Andrea Carmine" uniqKey="Belin A" first="Andrea Carmine" last="Belin">Andrea Carmine Belin</name><name sortKey="Dehem, Marie" sort="Dehem, Marie" uniqKey="Dehem M" first="Marie" last="Dehem">Marie Dehem</name><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A" last="Factor">Stewart A. Factor</name><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><name sortKey="Fiske, Brian K" sort="Fiske, Brian K" uniqKey="Fiske B" first="Brian K" last="Fiske">Brian K. Fiske</name><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M" last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><name sortKey="Higgins, Donald S" sort="Higgins, Donald S" uniqKey="Higgins D" first="Donald S" last="Higgins">Donald S. Higgins</name><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P A" last="Ioannidis">John P A. Ioannidis</name><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><name sortKey="Marder, Karen S" sort="Marder, Karen S" uniqKey="Marder K" first="Karen S" last="Marder">Karen S. Marder</name><name sortKey="Mayeux, Richard P" sort="Mayeux, Richard P" uniqKey="Mayeux R" first="Richard P" last="Mayeux">Richard P. Mayeux</name><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D" last="Mellick">George D. Mellick</name><name sortKey="Montimurro, Jennifer S" sort="Montimurro, Jennifer S" uniqKey="Montimurro J" first="Jennifer S" last="Montimurro">Jennifer S. Montimurro</name><name sortKey="Myers, Richard M" sort="Myers, Richard M" uniqKey="Myers R" first="Richard M" last="Myers">Richard M. Myers</name><name sortKey="Nelson, Lorene M" sort="Nelson, Lorene M" uniqKey="Nelson L" first="Lorene M" last="Nelson">Lorene M. Nelson</name><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G" last="Nutt">John G. Nutt</name><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name><name sortKey="Ritz, Beate" sort="Ritz, Beate" uniqKey="Ritz B" first="Beate" last="Ritz">Beate Ritz</name><name sortKey="Samii, Ali" sort="Samii, Ali" uniqKey="Samii A" first="Ali" last="Samii">Ali Samii</name><name sortKey="Southwick, Audrey" sort="Southwick, Audrey" uniqKey="Southwick A" first="Audrey" last="Southwick">Audrey Southwick</name><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline M" last="Tanner">Caroline M. Tanner</name><name sortKey="Trikalinos, Thomas A" sort="Trikalinos, Thomas A" uniqKey="Trikalinos T" first="Thomas A" last="Trikalinos">Thomas A. Trikalinos</name><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><name sortKey="Van Den Eeden, Stephen K" sort="Van Den Eeden, Stephen K" uniqKey="Van Den Eeden S" first="Stephen K" last="Van Den Eeden">Stephen K. Van Den Eeden</name><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P" last="Zabetian">Cyrus P. Zabetian</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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