Progressive supranuclear palsy (PSP) is a brain disease with tau aggregates in neurons, oligodendrocytes, and astrocytes. Previous work identified two genetic variants that elevate PSP risk. This study used whole exome sequencing to search for additional genetic risk factors. A collection of autopsy-confirmed PSP samples of European ancestry from approximately 20 sites across the United States were assembled. Over half are from the Mayo Clinic, Jacksonville. 764 PSP samples were sequenced initially, and additional sequencing was done for samples where coverage did not reach 20X coverage for more than 80% targeted region and 10X coverage for more than 90% of the targeted regions. 550 PSP samples passed quality checks.  WES data was processed using the Alzheimer’s Disease Sequencing Project (ADSP) protocol for quality control procedures and for generating a project level variant call format file (VCF).

Gerard D. Schellenberg, Ph.D.

Funded by CurePSP.

This work was funded by the following NIH grants: P01 AG017586 (VM-YL, GDS, JQT), U54 NS100693 (OR, DD, GDS), UG3 NS104095 (GDS, L-SW, OR), U54 AG052427 (l-SW, GDS), P30 AG010133 (B.G.), R01 AG057516 (AC, AM, AW, JAP, SG), R01 HL143790 (AC, SG), R01 HG010067 (SG), RF1 AG055477 (CB), P01 AG017586 (VM-YL, GDS, JQT, VMV), UG3 NS104095 and CWOW grant U54 NS100693 (DD), AG025688 and NS055077 (MG), P30 AG012300 (CLW), P30 AG053760 (APL and RA), 1P50NS091856 (RA), 5 P50 AG005134 (MPF), AG005131 (DRG), Johns Hopkins University Morris K. Udall Parkinson’s Disease Research Center of Excellence grant  P50 NS038377 and Alzheimer’s Disease Research Center grant P50 AG05146 (JCT), U24 NS072026 and P30 AG19610 (TGB). This work was also funded by Cure PSP (GDS), the Rainwater Foundation (GDS), the Daniel B. Burke Endowed Chair for Diabetes Research (SG), the CHOP Center for Spatial and Functional Genomics (AW, SFG), a CUREPSP research grant (Cure PSP Grant # 515-14; 2013-2015) to P.P., the Reta Lila Weston Trust for Medical Research, the PSP Association (RdS), and the Michael J. Fox Foundation for Parkinson’s Research (TGB). G. Höglinger was funded by the German Research Foundation (DFG) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the German Federal Ministry of Education and Research (BMBF, 01KU1403A EpiPD; 01EK1605A HitTau), and the NOMIS foundation (FTLD project). J. Hardy was partly funded by UKDRI limited which receives its funding from the MRC, the Alzheimer’s Society and Alzheimer Research UK. The London Neurodegenerative Diseases Brain Bank receives funding from the UK Medical Research Council (MR/L016397/1) and as part of the Brains for Dementia Research programme, jointly funded by Alzheimer’s Research UK and the Alzheimer’s Society. Queen Square Brain Bank is supported by the Reta Lila Weston Institute for Neurological Studies and the Medical Research Council UK. Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council (MR/L016451/1) and by Brains for Dementia Research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK (CMM) and National Institute of Health Research Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (CMM). This work was partly funded by UKDRI limited which receives its funding from the MRC, the Alzheimer’s Society and Alzheimer Research UK (JH). The Mayo Clinic Florida had support from a Morris K. Udall Parkinson’s Disease Research Center of Excellence (NINDS P50 #NS072187), CurePSP and the Tau Consortium. OAR is supported by a NINDS Tau Center without Walls (U54-NS100693), NINDS R01-NS078086 and the Mayo Clinic Center for Individualized Medicine. Funding provided by CurePSP through the generous support of the Peebler PSP Research Foundation in memory of Charles D. Peebler Jr. and Drs. Jeffrey S. and Jennifer R. Friedman in memory of Morton L. Friedman.