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@ARTICLE{Pottier:278068,
author = {Pottier, Cyril and Küçükali, Fahri and Baker, Matt and
Batzler, Anthony and Jenkins, Gregory D and van
Blitterswijk, Marka and Vicente, Cristina T and De Coster,
Wouter and Wynants, Sarah and Van de Walle, Pieter and Ross,
Owen A and Murray, Melissa E and Faura, Júlia and Haggarty,
Stephen J and van Rooij, Jeroen Gj and Mol, Merel O and
Hsiung, Ging-Yuek R and Graff, Caroline and Öijerstedt,
Linn and Neumann, Manuela and Asmann, Yan and McDonnell,
Shannon K and Baheti, Saurabh and Josephs, Keith A and
Whitwell, Jennifer L and Bieniek, Kevin F and Forsberg, Leah
and Heuer, Hilary and Lago, Argentina Lario and Geier, Ethan
G and Yokoyama, Jennifer S and Oddi, Alexis P and Flanagan,
Margaret and Mao, Qinwen and Hodges, John R and Kwok, John B
and Domoto-Reilly, Kimiko and Synofzik, Matthis and Wilke,
Carlo and Onyike, Chiadi and Dickerson, Bradford C and
Evers, Bret M and Dugger, Brittany N and Munoz, David G and
Keith, Julia and Zinman, Lorne and Rogaeva, Ekaterina and
Suh, EunRan and Gefen, Tamar and Geula, Changiz and
Weintraub, Sandra and Diehl-Schmid, Janine and Farlow,
Martin R and Edbauer, Dieter and Woodruff, Bryan K and
Caselli, Richard J and Donker Kaat, Laura L and Huey, Edward
D and Reiman, Eric M and Mead, Simon and King, Andrew and
Roeber, Sigrun and Nana, Alissa L and Ertekin-Taner, Nilufer
and Knopman, David S and Petersen, Ronald C and Petrucelli,
Leonard and Uitti, Ryan J and Wszolek, Zbigniew K and Ramos,
Eliana Marisa and Grinberg, Lea T and Tempini, Maria Luisa
Gorno and Rosen, Howard J and Spina, Salvatore and Piguet,
Olivier and Grossman, Murray and Trojanowski, John Q and
Keene, C Dirk and Jin, Lee-Way and Prudlo, Johannes and
Geschwind, Daniel H and Rissman, Robert A and Cruchaga,
Carlos and Ghetti, Bernardino and Halliday, Glenda M and
Beach, Thomas G and Serrano, Geidy E and Arzberger, Thomas
and Herms, Jochen and Boxer, Adam L and Honig, Lawrence S
and Vonsattel, Jean P and Lopez, Oscar L and Kofler, Julia
and White, Charles L and Gearing, Marla and Glass, Jonathan
and Rohrer, Jonathan D and Irwin, David J and Lee, Edward B
and Van Deerlin, Vivianna and Castellani, Rudolph and
Mesulam, Marsel M and Tartaglia, Maria C and Finger,
Elizabeth C and Troakes, Claire and Al-Sarraj, Safa and
Dalgard, Clifton L and Miller, Bruce L and Seelaar, Harro
and Graff-Radford, Neill R and Boeve, Bradley F and
Mackenzie, Ian Ra and van Swieten, John C and Seeley,
William W and Sleegers, Kristel and Dickson, Dennis W and
Biernacka, Joanna M and Rademakers, Rosa},
title = {{D}eciphering distinct genetic risk factors for
{FTLD}-{TDP} pathological subtypes via whole-genome
sequencing.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DZNE-2025-00559},
pages = {3914},
year = {2025},
abstract = {Frontotemporal lobar degeneration with neuronal inclusions
of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal
neurodegenerative disorder with only a limited number of
risk loci identified. We report our comprehensive
genome-wide association study as part of the International
FTLD-TDP Whole-Genome Sequencing Consortium, including 985
patients and 3,153 controls compiled from 26
institutions/brain banks in North America, Europe and
Australia, and meta-analysis with the Dementia-seq cohort.
We confirm UNC13A as the strongest overall FTLD-TDP risk
factor and identify TNIP1 as a novel FTLD-TDP risk factor.
In subgroup analyzes, we further identify genome-wide
significant loci specific to each of the three main FTLD-TDP
pathological subtypes (A, B and C), as well as enrichment of
risk loci in distinct tissues, brain regions, and neuronal
subtypes, suggesting distinct disease aetiologies in each of
the subtypes. Rare variant analysis confirmed TBK1 and
identified C3AR1, SMG8, VIPR1, RBPJL, L3MBTL1 and ANO9, as
novel subtype-specific FTLD-TDP risk genes, further
highlighting the role of innate and adaptive immunity and
notch signaling pathway in FTLD-TDP, with potential
diagnostic and novel therapeutic implications.},
keywords = {Humans / Genome-Wide Association Study / Whole Genome
Sequencing / Risk Factors / Genetic Predisposition to
Disease / Male / Female / Frontotemporal Lobar Degeneration:
genetics / Frontotemporal Lobar Degeneration: pathology /
DNA-Binding Proteins: genetics / DNA-Binding Proteins:
metabolism / Aged / Middle Aged / Brain: pathology / Brain:
metabolism / Protein Serine-Threonine Kinases: genetics /
Cohort Studies / Nerve Tissue Proteins: genetics /
DNA-Binding Proteins (NLM Chemicals) / Protein
Serine-Threonine Kinases (NLM Chemicals) / TARDBP protein,
human (NLM Chemicals) / TBK1 protein, human (NLM Chemicals)
/ Nerve Tissue Proteins (NLM Chemicals)},
cin = {AG Neumann / AG Gasser / AG Edbauer / AG Teipel / AG Herms},
ddc = {500},
cid = {I:(DE-2719)1210003 / I:(DE-2719)1210000 /
I:(DE-2719)1110004 / I:(DE-2719)1510100 /
I:(DE-2719)1110001},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40280976},
pmc = {pmc:PMC12032271},
doi = {10.1038/s41467-025-59216-0},
url = {https://pub.dzne.de/record/278068},
}