Do polymorphisms in the familial Parkinsonism genes contribute to risk for sporadic Parkinson's disease?
Recent whole genome association studies provided little evidence that polymorphisms at the familial Parkinsonism loci influence the risk for Parkinson's disease (PD). However, these studies are not designed to detect the types of subtle effects that common variants may impose. Here, we use an alternative targeted candidate gene approach to examine common variation in 11 genes related to familial Parkinsonism. PD cases (n = 331) and unaffected control subjects (n = 296) were recruited from three specialist movement disorder clinics in Brisbane, Australia and the Australian Electoral Roll. Common genetic variables (76 SNPs and 1 STR) were assessed in all subjects and haplotype, genotype, and allele associations explored. Modest associations (uncorrected P < 0.05) were observed for common variants around SNCA, UCHL1, MAPT, and LRRK2 although none were of sufficient magnitude to survive strict statistical corrections for multiple comparisons. No associations were seen for PRKN, PINK1, GBA, ATP13A2, HTRA2, NR4A2, and DJ1. Our findings suggest that common genetic variables of selected PD-related loci contribute modestly to PD risk in Australians.
Sutherland
Greg T
GT
Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular and Physical Sciences, Griffith University, Brisbane, Queensland, Australia.
Halliday
Glenda M
GM
Silburn
Peter A
PA
Mastaglia
Frank L
FL
Rowe
Dominic B
DB
Boyle
Richard S
RS
O'Sullivan
John D
JD
Ly
Tina
T
Wilton
Steve D
SD
Mellick
George D
GD
D000368:Aged; D001315:Australia / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D006180:Proton-Translocating ATPases / Q000235:genetics; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
D005962:Glucosylceramidase; D000074923:High-Temperature Requirement A Serine Peptidase 2; D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D024101:Mitochondrial Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D006180:Proton-Translocating ATPases; D012697:Serine Endopeptidases; D043222:Ubiquitin Thiolesterase; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D016875:tau Proteins; D000099202:PTEN-Induced Putative Kinase; C514983:ATP13A2 protein, human; C054369:MAPT protein, human; C497604:SNCA protein, human; C482860:UCHL1 protein, human; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human; C000615914:HTRA2 protein, human