EGAGenomicsIllumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001000973EGAEGA study EGAS00001000973Dataset for Parkinson's disease target re-sequencing projectEGArestrictedParkinson's disease (PD) can be divided into familial (Mendelian) and sporadic forms. A number of causal genes have been discovered for the Mendelian form, which constitutes 10-20% of the total cases. Genome-wide association studies have successfully uncovered a number of susceptibility loci for sporadic cases but those only explain a small fraction (6-7%) of PD heritability. It has been observed that some genes that confer susceptibility to PD through common risk variants also contain rare causing mutations for the Mendelian forms of the disease. These results suggest a possible functional link between Mendelian and sporadic PD and led us to investigate the role that rare and low-frequency variants could have on the sporadic form. Through a targeting approach, we have resequenced at 49× coverage the exons and regulatory regions of 38 genes (including Mendelian and susceptibility PD genes) in 249 sporadic PD patients and 145 unrelated controls of European origin. Unlike susceptibility genes, Mendelian genes show a clear general enrichment of rare functional variants in PD cases, observed directly as well as with Tajima's D statistic and several collapsing methods. Our findings suggest that rare variation on PD Mendelian genes may have a role in the sporadic forms of the disease.Mendelian genes for Parkinson's disease contribute to the sporadic forms of the disease.Spataro Nino N, Calafell Francesc F, Cervera-Carles Laura L, Casals Ferran F, Pagonabarraga Javier J, Pascual-Sedano Berta B, Campolongo Antònia A, Kulisevsky Jaime J, Lleó Alberto A, Navarro Arcadi A, Clarimón Jordi J, Bosch Elena EfalseHigh coverage target resequencing of coding and regulatory regions of 38 Parkinson disease genes associated either to the Mendelian or the sporadic forms of the diseaseCoding sequences and putative regulatory sequences (retrieved from Ensembl and including up to 2500 bp of promoter sequence upstream the transcription start site) were re-sequenced to a mean depth of 49X on 38 genes associated to Parkinson's disease (RAB25, NUCKS1, RAB7L1, GBA, SYT11, ACMSD, STK39, MCCC1, STBD1, GAK, DGKQ, BST1, SCARB2, HLA-DRB5, GPNMB, FGF20, ITGA8, HIP1R, STX1B, SETD1A, SREBF1, MED13, RAI1, MAPT, RIT2, GIGYF2, HTRA2, EIF4G1, SNCA, LRRK2, VPS35, PINK1, DJ1, ATP13A2, UCHL1, PARK2, FBXO7, and PLA2G6). Sequencing was performed on 249 Parkinson's idiopathic cases and 145 unrelated controls of Spanish origin. All sequencing data was generated with an Illumina Hiseq2000 instrument after enrichment with a custom NimbleGen array. Raw reads were mapped to human reference genome hg19/GRCh37 using BWA aligner.2017-07-26 15:39:25EGAS00001000973960625504046EGAD00001001029EGAC00001000244