Hopfner, F;
Mueller, SH;
Szymczak, S;
Junge, O;
Tittmann, L;
May, S;
Lohmann, K;
... Kuhlenbäumer, G; + view all
(2020)
Rare Variants in Specific Lysosomal Genes Are Associated with Parkinson's Disease.
Movement Disorders
10.1002/mds.28037.
(In press).
![[thumbnail of mds.28037.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/text.png) |
Text
mds.28037.pdf - Published Version Access restricted to UCL open access staff Download (265kB) |
Abstract
Objective: Impaired lysosomal degradation of α‐synuclein and other cellular constituents may play an important role in Parkinson's disease (PD). Rare genetic variants in the glucocerebrosidase (GBA) gene were consistently associated with PD. Here we examine the association between rare variants in lysosomal candidate genes and PD. / Methods: We investigated the association between PD and rare genetic variants in 23 lysosomal candidate genes in 4096 patients with PD and an equal number of controls using pooled targeted next‐generation DNA sequencing. Genewise association of rare variants in cases or controls was analyzed using the optimized sequence kernel association test with Bonferroni correction for the 23 tested genes. / Results: We confirm the association of rare variants in GBA with PD and report novel associations for rare variants in ATP13A2, LAMP1, TMEM175, and VPS13C. / Conclusion: Rare variants in selected lysosomal genes, first and foremost GBA, are associated with PD. Rare variants in ATP13A2 and VPC13C previously linked to monogenic PD and more common variants in TMEM175 and VPS13C previously linked to sporadic PD in genome‐wide association studies are associated with PD.
| Type: | Article |
|---|---|
| Title: | Rare Variants in Specific Lysosomal Genes Are Associated with Parkinson's Disease |
| DOI: | 10.1002/mds.28037 |
| Publisher version: | https://doi.org/10.1002/mds.28037 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | ATP13A2, chaperone‐mediated‐autophagy, GBA, LAMP1, Lysosme, Parkinson's disease, TMEM175, VPS13C, α‐synuclein |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10096573 |
Archive Staff Only
 |
View Item |
