Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study (original) (raw)

2006, The Lancet Neurology

Background A genome-wide association study identifi ed 13 single-nucleotide polymorphisms (SNPs) signifi cantly associated with Parkinson's disease. Small-scale replication studies were largely non-confi rmatory, 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 consortiacomprising 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 eff ects using fi xed and random eff ects models stratifi ed 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 fi xed and random-eff ects models no associations with any of the 13 SNPs were identifi ed (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 signifi cant 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 fi nding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease.