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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Evangelos Evangelou
  • Demetrius M. Maraganore
  • Grazia Annesi
  • Laura Brighina
  • Alexis Brice
  • Alexis Elbaz
  • Carlo Ferrarese
  • Georgios M. Hadjigeorgiou
  • Rejko Krueger
  • Jean-Charles Lambert
  • Suzanne Lesage
  • Katerina Markopoulou
  • George D. Mellick
  • Bram Meeus
  • Nancy L. Pedersen
  • Aldo Quattrone
  • Christine Van Broeckhoven
  • Manu Sharma
  • Peter A. Silburn
  • Eng-King Tan
  • Karin Wirdefeldt
  • John P A Ioannidis
  • Genetic Epidemiology of Parkinson's Disease (GEOPD) Consortium
Organisations
External organisations
  • University of Ioannina
  • Skåne University Hospital
  • Mayo Clinic Minnesota
  • CNR: National Research Council of Italy
  • University of Milano-Bicocca
  • Center For Immunology Of Viral Infections And Autoimmune Diseases
  • Pierre and Marie Curie University
  • University of Thessaly
  • University Hospital of Tubingen
  • Lille 2 University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics

Keywords

  • Genome-Wide Association Study, Humans, Parkinson Disease, Polymorphism, Genetic, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)220-8
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153B
Issue number1
Publication statusPublished - 2010 Jan 5
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Andreas Puschmann is part of Group Author