We conducted the largest PSP GWAS of the Iberian population to date (522 cases from 22 Spanish and Portuguese institutions). We independently replicated seven known PSP risk variants, and unveiled a novel locus in NFASC/CNTN2 after meta-analysing our results with a newly available Dutch cohort and publicly available summary statistics. These findings highlight the importance of neuron-oligodendrocyte interactions in PSP etiopathology.

Vigil Neuroscience and Prevail therapeutics are in a public-private partnerschip research program of Sven J. van der Lee. All funding is paid to his institution.

This work was funded by CIBERNED (Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas) 10th internal call for cooperative projects (Register number: 2019/09). Agustin Ruiz, Pascual Sanchez-Juan, Alberto Rabano, and Maria J. Bullido received funding from this convocatory. Pablo Garcia-Gonzalez received support by CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into ISCIII (Instituto de Salud Carlos III). Merce Boada, Marta Marquie and Agustin Ruiz are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240. PI19/01301, PI19/00335 and PI22/011403, and CIBERNED grant 2019/08. The Genome Research @ Fundacio ACE project (GR@ACE) is supported by Grifols SA, Fundacion bancaria La Caixa, Fundacio ACE, and CIBERNED. Accion Estrategica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII - Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER - Una manera de hacer Europa). Agustin Ruiz is supported by ISCIII national grant PMP22/00022, funded by the European Union (NextGenerationEU). The genotyping service to generate GR@ACE and PSP/DEGESCO GWAS data was carried out at CEGEN-PRB3-ISCIII; it is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. Itziar de Rojas received support by a national grant from ISCIII FI20/00215. Amanda Cano acknowledges the support of the Spanish Ministry of Science, Innovation and Universities under the grant Juan de la Cierva (FJC2018-036012-I), the support of ISCIII under the grant Sara Borrell (CD22/00125), Spanish Ministry of Science and Innovation, Proyectos de Generacion de Conocimiento grant PID2021-122473OA-I00, and Fundacion ADEY under the program Proyectos de Investigacion en Salud 2023. Fondo de Investigacion en Salud (Instituto Carlos III) (PI17/00096) in the frame of the European Regional Development Fund (ERDF) and to Fundacio ́ la Marato ́ de TV3 (PI043296 and 202009-10). This work was supported by the Spanish Ministry of Science and Innovation (RTC2019-007150-1), the Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (PI14/01823, PI16/01575, PI18/01898, PI19/01576, PI21/01875), the Consejeria de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia (CVI-02526, CTS-7685, PY20_00896), and the Consejeria de Salud y Bienestar Social de la Junta de Andalucia (PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019). Pilar Gomez-Garre was supported by the Nicolas Monardes program (C-0048-2017) from Andalusian Regional Ministry of Health. Laura Munoz-Delgado was supported by the Rio Hortega program [CM21/00051] from the Instituto de Salud Carlos III (ISCIII-FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sven J. van der Lee was funded for this study by NWO (#733050512, PROMO-GENODE: a PROspective study of MOnoGEnic causes Of Dementia) a substantial donation by Edwin Bouw Fonds and Dioraphte. SvdL further received funding for the GeneMINDS consortium, which is powered by Health-Holland, Top Sector Life Sciences & Health. Sven J. van der Lee is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. ABOARD also receives funding from de Hersenstichting, Edwin Bouw Fonds and Gieskes-Strijbisfonds. Array genotyping was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061). This work has been supported by the Queen Sofia Foundation. Pascual Sanchez-Juan is supported by grants from ISCIII (PMP22/00022 and PI20/01011) and TED2021-131676B-100. Luis Miguel Real received support from The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study). Consejeria de Salud de la Junta de Andalucia (grant number PI-0001/2017) and CIBERINFEC -Consorcio Centro de Investigacion Biomedica en Red de Enfermedades Infecciosas- Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion y Union Europea (Spain) (NextGeneration EU) (grant number CB21/13/00118). Jose Luis Royo received support from Project 23.04.2021 from Santangela Foundation (Sevilla, Spain).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

For the Iberian cohort, this study was approved by the competent research ethical committee (MED-FACE-2020-01, Universidad Internacional de Catalunya, Sant Cugat del Valles, Spain). For the Dutch cohorts, the local Medical Ethics Committees approved the protocols for the Amsterdam Dementia Cohort (ADC) and the other studies, and all participants of the ADC provided written informed consent.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.