A Case-Control Association Study of the 12 Single-Nucleotide Polymorphisms Implicated in Parkinson Disease by a Recent Genome Scan

Abstract

a The top 11 markers are presented in the same order as in table 4 in Maraganore et al. 1 b Counts of genotype 11, 12, and 22. c Minor-allele frequency. d Two-sided P value for all strata and for female and male substrata in rs7878232.

Investigation of the PARK10 Gene in Parkinson Disease

“…Our current study, along with three other recent reports (Farrer et al 2006;Goris et al 2006;Li et al 2006), provides sufficient evidence to diminish the possibility that CDCP2 is the PARK10 gene. Meanwhile, the question of whether HIVEP3 is the PARK10 gene has grown more interesting.…”

“…They did not find any significant association evidence for these SNPs. Goris et al (2006) and Li et al (2006) repeated the previously reported CDCP2 SNPs on unrelated case-control samples (sample size > 600 on both studies), but neither SNP showed significant association with PD. Unfortunately, HIVEP3 was not included in these investigations.…”

“…The drawbacks of CDCP2 as the PARK10 gene were demonstrated by three recent follow-up studies (Farrer et al 2006;Goris et al 2006;Li et al 2006). None of these studies successfully replicated the WGA results including the CDCP2 association, supporting the previous negative finding of Oliveria et al Farrer et al (2006) genotyped 28 SNPs within a 132-kb region surrounding CDCP2 on 676 Norwegian, 372 Irish, and 522 US unrelated case-control samples.…”

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

“…In meta-analyses including our data as well as the tier-two data from the original wholegenome association study 2 and several smaller replication studies, [3][4][5][6][7] none of the 13 SNPs showed nominally significant association even at p>0·064; all summary ORs were between 0·95 and 1·08 with 95% CIs excluding ORs smaller than 0·87 or larger than 1·18. Heterogeneity was formally significant only for SNP13 (p=0·03, I 2 =34%).…”

“…2 After the publication of that study, several investigators tried to replicate one or more of these associations. [3][4][5][6][7] The results of these follow-up studies have been largely non-confirmatory, leading to much controversy. 8,9 In view of the importance of understanding the contribution of genetics to Parkinson's disease and the desire to provide further clarity to this research area, The Michael J Fox Foundation for Parkinson's Research, which funded the original genome-wide study, coordinated its own independent large-scale multicentre international replication effort.…”