dc.date.accessioned | 2018-07-23T12:01:20Z | |
dc.date.available | 2018-08-19T22:31:23Z | |
dc.date.created | 2017-11-25T17:13:00Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Berge-Seidl, Victoria Pihlstrøm, Lasse Maple-Grødem, Jodi Forsgren, Lars Linder, Jan Larsen, Jan Petter Tysnes, Ole-Bjørn Toft, Harald Mathias Strøm . The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal. Neuroscience Letters. 2017, 658, 48-52 | |
dc.identifier.uri | http://hdl.handle.net/10852/62416 | |
dc.description.abstract | Objective: Coding variants in the GBA gene have been identified as the numerically most important genetic risk factors for Parkinson's disease (PD). In addition, genome-wide association studies (GWAS) have identified associations with PD in the SYT11-GBA region on chromosome 1q22, but the relationship to GBA coding variants have remained unclear. The aim of this study was to sequence the complete GBA gene in a clinical cohort and to investigate whether coding variants within the GBA gene may be driving reported association signals.
Methods: We analyzed high-throughput sequencing data of all coding exons of GBA in 366 patients with PD. The identified low-frequency coding variants were genotyped in three Scandinavian case-controls series (786 patients and 713 controls). Previously reported risk variants from two independent association signals within the SYT11-GBA locus on chromosome 1 were also genotyped in the same samples. We performed association analyses and evaluated linkage disequilibrium (LD) between the variants.
Results: We identified six rare mutations (1.6%) and two low-frequency coding variants in GBA. E326K (rs2230288) was significantly more frequent in PD patients compared to controls (OR 1.65, p = 0.03). There was no clear association of T369M (rs75548401) with disease (OR 1.43, p = 0.24). Genotyping the two GWAS hits rs35749011 and rs114138760 in the same sample set, we replicated the association between rs35749011 and disease status (OR 1.67, p = 0.03), while rs114138760 was found to have similar allele frequencies in patients and controls. Analyses revealed that E326K and rs35749011 are in very high LD (r2 0.95).
Conclusions: Our results confirm that the GBA variant E326K is a susceptibility allele for PD. The results suggest that E326K may fully account for the primary association signal observed at chromosome 1q22 in previous GWAS of PD. | en_US |
dc.language | EN | |
dc.publisher | Elsevier Science | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Berge-Seidl, Victoria | |
dc.creator.author | Pihlstrøm, Lasse | |
dc.creator.author | Maple-Grødem, Jodi | |
dc.creator.author | Forsgren, Lars | |
dc.creator.author | Linder, Jan | |
dc.creator.author | Larsen, Jan Petter | |
dc.creator.author | Tysnes, Ole-Bjørn | |
dc.creator.author | Toft, Harald Mathias Strøm | |
cristin.unitcode | 185,53,42,13 | |
cristin.unitname | Nevrologisk avdeling | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1518381 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Neuroscience Letters&rft.volume=658&rft.spage=48&rft.date=2017 | |
dc.identifier.jtitle | Neuroscience Letters | |
dc.identifier.volume | 658 | |
dc.identifier.startpage | 48 | |
dc.identifier.endpage | 52 | |
dc.identifier.doi | http://dx.doi.org/10.1016/j.neulet.2017.08.040 | |
dc.identifier.urn | URN:NBN:no-64993 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0304-3940 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/62416/1/Berge-Seidl_et_al.pdf | |
dc.type.version | AcceptedVersion | |