Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing
- Jansen, I.E.
- Ye, H.
- Heetveld, S.
- Lechler, M.C.
- Michels, H.
- Seinstra, R.I.
- Lubbe, S.J.
- Drouet, V.
- Lesage, S.
- Majounie, E.
- Gibbs, J.R.
- Nalls, M.A.
- Ryten, M.
- Botia, J.A.
- Vandrovcova, J.
- Simon-Sanchez, J.
- Castillo-Lizardo, M.
- Rizzu, P.
- Blauwendraat, C.
- Chouhan, A.K.
- Li, Y.
- Yogi, P.
- Amin, N.
- Duijn, C.M. van
- Morris, H.R.
- Brice, A.
- Singleton, A.B.
- David, D.C.
- Nollen, E.A.
- Jain, S.
- Shulman, J.M.
- Heutink, P.
- Bloem, B.
- Post, B.
- Scheffer, H.
- Warrenburg, B.P.C. van de
- et al.
DOIAbstract
BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings wer...
Add to ORKG