TY - JOUR
T1 - Association studies of sporadic Parkinson's disease in the genomic era
AU - Labbé, Catherine
AU - Ross, Owen A.
PY - 2014
Y1 - 2014
N2 - Parkinson's disease is a common age-related progressive neurodegenerative disorder. Over the last 10 years, advances have been made in our understanding of the etiology of the disease with the greatest insights perhaps coming from genetic studies, including genome-wide association approaches. These large scale studies allow the identification of genomic regions harboring common variants associated to disease risk. Since the first genome-wide association study on sporadic Parkinson's disease performed in 2005, improvements in study design, including the advent of meta-analyses, have allowed the identification of ~21 susceptibility loci. The first loci to be nominated were previously associated to familial PD (SNCA, MAPT, LRRK2) and these have been extensively replicated. For other more recently identified loci (SREBF1, SCARB2, RIT2) independent replication is still warranted. Cumulative risk estimates of associated variants suggest that more loci are still to be discovered. Additional association studies combined with deep re-sequencing of known genome-wide association study loci are necessary to identify the functional variants that drive disease risk. As each of these associated genes and variants are identified they will give insight into the biological pathways involved the etiology of Parkinson's disease. This will ultimately lead to the identification of molecules that can be used as biomarkers for diagnosis and as targets for the development of better, personalized treatment.
AB - Parkinson's disease is a common age-related progressive neurodegenerative disorder. Over the last 10 years, advances have been made in our understanding of the etiology of the disease with the greatest insights perhaps coming from genetic studies, including genome-wide association approaches. These large scale studies allow the identification of genomic regions harboring common variants associated to disease risk. Since the first genome-wide association study on sporadic Parkinson's disease performed in 2005, improvements in study design, including the advent of meta-analyses, have allowed the identification of ~21 susceptibility loci. The first loci to be nominated were previously associated to familial PD (SNCA, MAPT, LRRK2) and these have been extensively replicated. For other more recently identified loci (SREBF1, SCARB2, RIT2) independent replication is still warranted. Cumulative risk estimates of associated variants suggest that more loci are still to be discovered. Additional association studies combined with deep re-sequencing of known genome-wide association study loci are necessary to identify the functional variants that drive disease risk. As each of these associated genes and variants are identified they will give insight into the biological pathways involved the etiology of Parkinson's disease. This will ultimately lead to the identification of molecules that can be used as biomarkers for diagnosis and as targets for the development of better, personalized treatment.
KW - Genetics
KW - Genome-wide association studies
KW - Sporadic Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84896378136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896378136&partnerID=8YFLogxK
U2 - 10.2174/1389202914666131210212745
DO - 10.2174/1389202914666131210212745
M3 - Article
AN - SCOPUS:84896378136
SN - 1389-2029
VL - 15
SP - 2
EP - 10
JO - Current Genomics
JF - Current Genomics
IS - 1
ER -