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Do polymorphisms in the familial Parkinsonism genes contribute to risk for sporadic Parkinson's disease?
Author(s) -
Sutherland Greg T.,
Halliday Glenda M.,
Silburn Peter A.,
Mastaglia Frank L.,
Rowe Dominic B.,
Boyle Richard S.,
O'Sullivan John D.,
Ly Tina,
Wilton Steve D.,
Mellick George D.
Publication year - 2009
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.22214
Subject(s) - parkinsonism , lrrk2 , haplotype , parkinson's disease , genetics , single nucleotide polymorphism , disease , candidate gene , genotype , genetic association , allele , case control study , statistical genetics , biology , medicine , gene , pharmacogenetics
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. © 2009 Movement Disorder Society

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