Genomewide association study for onset age in Parkinson disease
Coordinators and Molecular Genetic Laboratories
MetadataShow full item record
BACKGROUND: Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. METHODS: Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. RESULTS: Meta-analysis across the three studies detected consistent association (p < 1 x 10(-5)) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 x 10(-7)) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 x 10(-6)) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. CONCLUSION: Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis.
Showing items related by title, author, creator and subject.
Sensation seeking, traumatic stress and coping: An empirical investigation in rescue forces = Sensation Seeking, Traumaerleben und Bewältigungsstrategien: eine empirische Untersuchung an Einsatzkräften Tschiesner R (2012)This investigation deals with sensation seeking in rescue forces. We are interested in the scores regarding this variable and relationship between these and other relevant variables. Aim of this research is to find connections ...
Hasan SMK; Schiraldi A; Cosio MS; Scampicchio M (2016)Common spectrometric methods to determine hydrogen peroxide scavenging activity require time-consuming extraction protocols and become poorly reliable because of the sample turbidity or the presence of UV-absorbing compounds. ...