Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease: large-scale collaborative study.

Evangelos Evangelou; Demetrius Maraganore; Grazia Annesi; Laura Brighina; Alexis Brice; Alexis Elbaz; Carlo Ferrarese; Georgios Hadjigeorgiou; Rejko Krueger; Jean-Charles Lambert; Suzanne Lesage; Katerina Markopoulou; George Mellick; Bram Meeus; Nancy Pedersen; Aldo Quattrone; Christine van Broeckhoven; Manu Sharma; Peter Silburn; Eng-King Tan; Karin Wirdefeldt; John Ioannidis

doi:10.1002/ajmg.b.30980

Journal articles

Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease: large-scale collaborative study.

Evangelos Evangelou ^{1, 2} Demetrius Maraganore ³ Grazia Annesi ⁴ Laura Brighina ⁵ Alexis Brice ⁶ Alexis Elbaz ⁷ Carlo Ferrarese ⁵ Georgios Hadjigeorgiou ^{8, 9} Rejko Krueger ¹⁰ Jean-Charles Lambert ¹¹ Suzanne Lesage ⁶ Katerina Markopoulou ⁸ George Mellick ¹² Bram Meeus ^{13, 14, 15} Nancy Pedersen ¹⁶ Aldo Quattrone ¹⁷ Christine van Broeckhoven ^{13, 15} Manu Sharma ¹⁰ Peter Silburn ¹² Eng-King Tan ^{18, 19} Karin Wirdefeldt ¹⁶ John Ioannidis ^{1, 20, 21, *}

* Corresponding author

1 Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology

2 Institute of Microbiology

3 Department of Neurology

4 Institute of Neurological Sciences

5 Section of Neurology

6 Neurologie et thérapeutique expérimentale

7 Neuroépidémiologie

8 Laboratory of Neurogenetics, Deparment of Neurology

9 Institute of Biomedical Research & Technology

10 Department of Neurology

11 Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations

12 Eskitis Institute for Cell and Molecular Therapies

13 Neurodegenerative Brain Diseases Group

14 Laboratory of Neurogenetics

15 UA - University of Antwerp

16 MEB - Department of Medical Epidemiology and Biostatistics

17 Institute of Neurology

18 Duke-NUS Medical School [Singapore]

19 Department of Neurology

20 Biomedical Research Institute

21 Institute for Clinical Research and Health Policy Studies

Abstract : Early genome-wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta-analysis of the first two GWA investigations might be replicable in different populations. We examined six single-nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the "Genetic Epidemiology of Parkinson's Disease" (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98-1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Neurons and Cognition [q-bio.NC]

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Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease: large-scale collaborative study.

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Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease: large-scale collaborative study.

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