TY - JOUR AU - Wang, Hui AU - Chang, Timothy S AU - Dombroski, Beth A AU - Cheng, Po-Liang AU - Si, Ya-Qin AU - Tucci, Albert AU - Patil, Vishakha AU - Valiente-Banuet, Leopoldo AU - Li, Chong AU - Farrell, Kurt AU - Mclean, Catriona AU - Molina-Porcel, Laura AU - Rajput, Alex AU - De Deyn, Peter Paul AU - Le Bastard, Nathalie AU - Gearing, Marla AU - Donker Kaat, Laura AU - Van Swieten, John C AU - Dopper, Elise AU - Ghetti, Bernardino F AU - Newell, Kathy L AU - Troakes, Claire AU - de Yébenes, Justo G AU - Rábano-Gutierrez, Alberto AU - Meller, Tina AU - Oertel, Wolfgang H AU - Respondek, Gesine AU - Stamelou, Maria AU - Arzberger, Thomas AU - Roeber, Sigrun AU - Müller, Ulrich AU - Hopfner, Franziska AU - Pastor, Pau AU - Brice, Alexis AU - Durr, Alexandra AU - Le Ber, Isabelle AU - Beach, Thomas G AU - Serrano, Geidy E AU - Hazrati, Lili-Naz AU - Litvan, Irene AU - Rademakers, Rosa AU - Ross, Owen A AU - Galasko, Douglas AU - Boxer, Adam L AU - Miller, Bruce L AU - Seeley, Willian W AU - Van Deerlin, Vivianna M AU - Lee, Edward B AU - White, Charles L AU - Morris, Huw R AU - de Silva, Rohan AU - Crary, John F AU - Goate, Alison M AU - Friedman, Jeffrey S AU - Compta, Yaroslau AU - Leung, Yuk Yee AU - Coppola, Giovanni AU - Naj, Adam C AU - Wang, Li-San AU - Dalgard, Clifton AU - Dickson, Dennis W AU - Höglinger, Günter U AU - Tzeng, Jung-Ying AU - Geschwind, Daniel H AU - Schellenberg, Gerard D AU - Lee, Wan-Ping TI - Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells. JO - Movement disorders VL - 40 IS - 5 SN - 0885-3185 CY - New York, NY PB - Wiley M1 - DZNE-2025-00623 SP - 950 - 961 PY - 2025 AB - The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).To investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.Utilizing whole genome sequencing data from 1684 PSP cases and 2392 controls, the three large CNVs (α, β, and γ) and structural forms within 17q21.31 were identified and analyzed for their association with PSP.We found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, P = 0.0018). From H1β1γ1 (OR = 1.21) and H1β2γ1 (OR = 1.24) to H1β1γ4 (OR = 1.57), structural forms of H1 with additional copies of γ displayed a higher risk for PSP. The frequency of the risk sub-haplotype H1c rises from 1 KW - Humans KW - Supranuclear Palsy, Progressive: genetics KW - DNA Copy Number Variations: genetics KW - Female KW - Male KW - Chromosomes, Human, Pair 17: genetics KW - Aged KW - Haplotypes: genetics KW - Neurons: metabolism KW - Genetic Predisposition to Disease: genetics KW - Middle Aged KW - Gene Expression KW - 17q21.31 (Other) KW - H1 and H2 haplotypes (Other) KW - copy number variations (Other) KW - progressive supranuclear palsy (Other) KW - single‐cell gene expression (Other) LB - PUB:(DE-HGF)16 C2 - pmc:PMC12089919 C6 - pmid:40055946 DO - DOI:10.1002/mds.30150 UR - https://pub.dzne.de/record/278787 ER -