TY - JOUR
T1 - Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease
T2 - a large-scale international study
AU - Elbaz, Alexis
AU - Nelson, Lorene M.
AU - Payami, Haydeh
AU - Ioannidis, John PA
AU - Fiske, Brian K.
AU - Annesi, Grazia
AU - Carmine Belin, Andrea
AU - Factor, Stewart A.
AU - Ferrarese, Carlo
AU - Hadjigeorgiou, Georgios M.
AU - Higgins, Donald S.
AU - Kawakami, Hideshi
AU - Krüger, Rejko
AU - Marder, Karen S.
AU - Mayeux, Richard P.
AU - Mellick, George D.
AU - Nutt, John G.
AU - Ritz, Beate
AU - Samii, Ali
AU - Tanner, Caroline M.
AU - Van Broeckhoven, Christine
AU - Van Den Eeden, Stephen K.
AU - Wirdefeldt, Karin
AU - Zabetian, Cyrus P.
AU - Dehem, Marie
AU - Montimurro, Jennifer S.
AU - Southwick, Audrey
AU - Myers, Richard M.
AU - Trikalinos, Thomas A.
N1 - Funding Information:
Investigators from three existing Edmond J Safra Global Genetics Consortia funded by The Michael J Fox Foundation for Parkinson's Research were invited to participate ( table 1 ). 10,11 Investigators involved in the original genome-wide study 2 were not invited in order to maintain independence between the two studies.
Funding Information:
BF is employed by The Michael J Fox Foundation for Parkinson's Research, which funded the study. MD is employed by Genoscreen, which has received funding from the Michael J Fox Foundation for Parkinson's Research. All other authors have no conflicts of interest.
Funding Information:
We thank the laboratory of Dr Matthew Farrer (Neurogenetic Laboratories, Udall Parkinson's Disease Research Center of Excellence, Mayo Clinic, Jacksonville, FL, USA) for providing details regarding TaqMan SNP Genotyping Assays for the 13 SNPs. Funding primarily to cover genotyping costs for the current study was provided to the three genetic consortia by The Michael J Fox Foundation for Parkinson's Research through a generous gift from the Edmond J Safra Philanthropic Foundation. Additional funding to individual investigators for other aspects of the original studies (eg, original sample collection and other support costs) was provided by: INSERM and the French Ministry of Environment (AE, PA, JCL, CT); NIH NS R01-31964 and Tobacco-Related Disease Research Fund Grant 8RT-0131 (LN); NIH NS R01-36960 and AG 08017 (HP); Swedish Research Council, Swedish Brain Foundation and the Hållsten Foundation, The Swedish Parkinson Foundation, Swedish Brain Power (ACB, DG, LO, OS, MW); German Ministry of Education and Research, Program NGFN2, No. 01GS0468 (RKr); National Parkinson Foundation (JN); US Department of Veterans Affairs Parkinson Disease Research Education and Clinical Center grant (ASa); the Special Research Fund of the University of Antwerp, the Fund for Scientific Research Flanders an EU contract LSHMCT-2003-503330 (CVB, PC, PDD, KN, PP, BP, JT); NIH Grant ES10758 (KW); NIH K08-NS044138; and a Veterans Affairs Merit Review Award (CZ).
PY - 2006/11
Y1 - 2006/11
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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.
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U2 - 10.1016/S1474-4422(06)70579-8
DO - 10.1016/S1474-4422(06)70579-8
M3 - Article
C2 - 17052658
AN - SCOPUS:33749667971
VL - 5
SP - 917
EP - 923
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4422
IS - 11
ER -