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. 2018 Jul 9;13(1):37.
doi: 10.1186/s13024-018-0267-3.

Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci

Monica Y Sanchez-Contreras  1   2 , Naomi Kouri  1 , Casey N Cook  1 , Daniel J Serie  3   4 , Michael G Heckman  3   4 , NiCole A Finch  1 , Richard J Caselli  5 , Ryan J Uitti  6 , Zbigniew K Wszolek  6 , Neill Graff-Radford  6 , Leonard Petrucelli  1 , Li-San Wang  7 , Gerard D Schellenberg  7 , Dennis W Dickson  1 , Rosa Rademakers  1 , Owen A Ross  8   9
Affiliations

Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci

Monica Y Sanchez-Contreras et al. Mol Neurodegener. .

Abstract

Background: Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is largely considered to be a sporadic disorder, cases with suspected familial inheritance have been identified and the common MAPT H1haplotype is a major genetic risk factor. Due to the relatively low prevalence of PSP, large sample sizes can be difficult to achieve, and this has limited the ability to detect true genetic risk factors at the genome-wide statistical threshold for significance in GWAS data. With this in mind, in this study we genotyped the genetic variants that displayed the strongest degree of association with PSP (P<1E-4) in the previous GWAS in a new cohort of 533 pathologically-confirmed PSP cases and 1172 controls, and performed a combined analysis with the previous GWAS data.

Results: Our findings validate the known association of loci at MAPT, MOBP, EIF2AK3 and STX6 with risk of PSP, and uncover novel associations with SLCO1A2 (rs11568563) and DUSP10 (rs6687758) variants, both of which were classified as non-significant in the original GWAS.

Conclusions: Resolving the genetic architecture of PSP will provide mechanistic insights and nominate candidate genes and pathways for future therapeutic intervention strategies.

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Conflict of interest statement

Ethics approval and consent to participate

Study subjects were recruited through protocols approved by the Mayo Clinic institutional review board and provided consent to participate.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Circos plot summarizing PSP meta-analysis results. The meta-analysis effect of each SNP is plotted in an adjusted scale (meta-analysis effect × 1000). The direction of association is shown with different colors: same direction in both analyses as red lines and opposite direction of association in both analyses as green lines
See this image and copyright information in PMC

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