Genome-wide association study confirms extant PD risk loci among the Dutch.

Javier Simón-Sánchez (1) , Jacobus J van Hilten (1) , Bart C.P. van de Warrenburg (1) , Henk W Berendse (1) , Sampath Arepalli (1) , Dena G Hernandez (1) , Rob M.A de Bie (1) , Daan Velseboer (1) , Hans Scheffer (1) , Bastiaan Bloem (1) , Karin D van Dijk (1) , Fernando Rivadeneira (1) , Albert Hofman (1) , André G A.Uitterlinden (1) , Patrizia Rizzu (1) , Z Bochdanovits (1) , Andrew Singleton (1) , Peter Heutink (1) , Bart Post (1)

1 Department of Clinical Genetics

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2,024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: p = 1.63 x 10-5, OR = 1.325 and BST1, rs12502586: p = 1.63 x 10-3, OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: p = 1.22 x 10-4, OR = 1.51; HLA, rs4248166: p = 4.39 x 10-5, OR = 1.36; and MAPT, rs3785880: p = 1.9 x 10-3, OR = 1.19).

Mots clés: Parkinson; SNCA; BST1

Javier Simón-Sánchez, Jacobus J van Hilten, Bart C.P. van de Warrenburg, Henk W Berendse, Sampath Arepalli, et al.. Genome-wide association study confirms extant PD risk loci among the Dutch.. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2010.254⟩. ⟨hal-00609412⟩