Genome-wide association study confirms extant PD risk loci among the Dutch.
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 2024 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 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 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 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).
Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands. j.simonsanchez@vumc.nl
Javier
J
Simón-Sánchez
Jacobus J
JJ
van Hilten
Bart
B
van de Warrenburg
Bart
B
Post
Henk W
HW
Berendse
Sampath
S
Arepalli
Dena G
DG
Hernandez
Rob M A
RM
de Bie
Daan
D
Velseboer
Hans
H
Scheffer
Bas
B
Bloem
Karin D
KD
van Dijk
Fernando
F
Rivadeneira
Albert
A
Hofman
André G
AG
Uitterlinden
Patrizia
P
Rizzu
Zoltan
Z
Bochdanovits
Andrew B
AB
Singleton
Peter
P
Heutink
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D016022:Case-Control Studies; D016172:DNA Fingerprinting; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012307:Risk Factors; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics*; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics*
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C486325:GAK protein, human; D017346:Protein Serine-Threonine Kinases; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2
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