Objective: The primary outcome of our study was the identification of rare variants in 5 major Mendelian PD genes (SNCA, PARK2, PINK1, DJ1, LRRK2) and the 2 more significant GWAS loci associated with PD (GBA and MAPT).

Background: Eighteen loci (PARK1-PARK18), either causing familial Parkinson’s disease (PD) or that increase consistently the risk for developing the disease have been identified. However, most genetic studies in PD have focused on a single gene in small case-control series.

Methods: We conducted pooled-DNA next generation targeted sequencing of SNCA, PARK2, PINK1, DJ1, LRRK2, GBA and MAPT genes in a large PD Spanish cohort (n=612; 165 with familial PD and 45 with early-onset PD). The European American population in the Exome Sequencing Project was used as a reference dataset to compare population-based allele frequencies.

Results: 58 variants were initially identified being a total of 48 validated including 7 novel. 27.12% of the sample (n=166) carried at least one variant, 2.78% (n=17) carried two variants and 0.16% (n=1) three variants. 27.08% (13/48) of all the variants were found in PARK2, 22.92% (11/48) of all the variants were found in LRRK2, 22.92% (11/48) found in GBA, 16.67% (8/48) in PINK1, 6.25% (3/48) in MAPT and 4.17% (2/48) in DJ1. After multiple test correction (p <0.001; 0.05/48), 17 variants showed a statistically significant association with the disease.

Conclusions: These results provide a realistic genetic landscape of an outpatient PD population and highlights the significant presence of new undiscovered and known variants in PD-causing and in susceptibility PD genes which are responsible for about 30% of the etiology in our sample.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/high-throughput-pooled-dna-sequencing-of-mendeliansusceptibility-parkinsons-disease-genes-in-spanish-population/