UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia

Lianne M. Reus; Sean W. Willemse; Sterre C.M. de Boer; Julie De Houwer; Willem L. Hartog; Merel O. Mol; Jeroen G.J. van Rooij; Niccolo Tesi; Laura Donker Kaat; Marc Hulsman; Everard G.B. Vijverberg; Henne Holstege; Wouter van Rheenen; Jan H. Veldink; Leonard H. van den Berg; John C. van Swieten; H. Seelaar; Sven J. van der Lee; Michael A. van Es; Yolande A.L. Pijnenburg

doi:10.1002/ana.27245

UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia

Lianne M. Reus, Sean W. Willemse, Sterre C.M. de Boer, Julie De Houwer, Willem L. Hartog, Merel O. Mol, Jeroen G.J. van Rooij, Niccolo Tesi, Laura Donker Kaat, Marc Hulsman, Everard G.B. Vijverberg, Henne Holstege, Wouter van Rheenen, Jan H. Veldink, Leonard H. van den Berg, John C. van Swieten, H. Seelaar, Sven J. van der Lee, Michael A. van Es^*, Yolande A.L. Pijnenburg

^*Corresponding author for this work

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Abstract

UNC13A (rs12608932-CC) is associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and shortens survival in ALS. We aim to describe the association for UNC13A and survival in FTD. We included 626 patients with FTD from Dutch memory clinics, including a subcohort of 150 patients with TDP-43 pathology. Survival analyses were performed using Cox proportional hazard models in a recessive manner. Homozygosity for rs12608932-C in UNC13A was associated with a shorter survival compared with other genotypes (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.02–1.60, p = 0.033), which has implications for patient counselling and trial design. ANN NEUROL 2025;97:1062–1066.

Original language	English
Pages (from-to)	1062-1066
Number of pages	5
Journal	Annals of Neurology
Volume	97
Issue number	6
Early online date	11 Apr 2025
DOIs	https://doi.org/10.1002/ana.27245
Publication status	Published - Jun 2025

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Reus, L. M., Willemse, S. W., de Boer, S. C. M., De Houwer, J., Hartog, W. L., Mol, M. O., van Rooij, J. G. J., Tesi, N., Donker Kaat, L., Hulsman, M., Vijverberg, E. G. B., Holstege, H., van Rheenen, W., Veldink, J. H., van den Berg, L. H., van Swieten, J. C., Seelaar, H., van der Lee, S. J., van Es, M. A., & Pijnenburg, Y. A. L. (2025). UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia. Annals of Neurology, 97(6), 1062-1066. https://doi.org/10.1002/ana.27245

@article{7e5707eae2124ad5a9a95f2656a33fbc,

title = "UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia",

abstract = "UNC13A (rs12608932-CC) is associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and shortens survival in ALS. We aim to describe the association for UNC13A and survival in FTD. We included 626 patients with FTD from Dutch memory clinics, including a subcohort of 150 patients with TDP-43 pathology. Survival analyses were performed using Cox proportional hazard models in a recessive manner. Homozygosity for rs12608932-C in UNC13A was associated with a shorter survival compared with other genotypes (hazard ratio [HR] = 1.28, 95\% confidence interval [CI] = 1.02–1.60, p = 0.033), which has implications for patient counselling and trial design. ANN NEUROL 2025;97:1062–1066.",

author = "Reus, \{Lianne M.\} and Willemse, \{Sean W.\} and \{de Boer\}, \{Sterre C.M.\} and \{De Houwer\}, Julie and Hartog, \{Willem L.\} and Mol, \{Merel O.\} and \{van Rooij\}, \{Jeroen G.J.\} and Niccolo Tesi and \{Donker Kaat\}, Laura and Marc Hulsman and Vijverberg, \{Everard G.B.\} and Henne Holstege and \{van Rheenen\}, Wouter and Veldink, \{Jan H.\} and \{van den Berg\}, \{Leonard H.\} and \{van Swieten\}, \{John C.\} and H. Seelaar and \{van der Lee\}, \{Sven J.\} and \{van Es\}, \{Michael A.\} and Pijnenburg, \{Yolande A.L.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2025",

month = jun,

doi = "10.1002/ana.27245",

language = "English",

volume = "97",

pages = "1062--1066",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley \& Sons Inc.",

number = "6",

}

Reus, LM, Willemse, SW, de Boer, SCM, De Houwer, J, Hartog, WL, Mol, MO, van Rooij, JGJ, Tesi, N, Donker Kaat, L, Hulsman, M, Vijverberg, EGB, Holstege, H, van Rheenen, W , Veldink, JH , van den Berg, LH, van Swieten, JC, Seelaar, H, van der Lee, SJ, van Es, MA & Pijnenburg, YAL 2025, 'UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia', Annals of Neurology, vol. 97, no. 6, pp. 1062-1066. https://doi.org/10.1002/ana.27245

TY - JOUR

T1 - UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia

AU - Reus, Lianne M.

AU - Willemse, Sean W.

AU - de Boer, Sterre C.M.

AU - De Houwer, Julie

AU - Hartog, Willem L.

AU - Mol, Merel O.

AU - van Rooij, Jeroen G.J.

AU - Tesi, Niccolo

AU - Donker Kaat, Laura

AU - Hulsman, Marc

AU - Vijverberg, Everard G.B.

AU - Holstege, Henne

AU - van Rheenen, Wouter

AU - Veldink, Jan H.

AU - van den Berg, Leonard H.

AU - van Swieten, John C.

AU - Seelaar, H.

AU - van der Lee, Sven J.

AU - van Es, Michael A.

AU - Pijnenburg, Yolande A.L.

PY - 2025/6

Y1 - 2025/6

N2 - UNC13A (rs12608932-CC) is associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and shortens survival in ALS. We aim to describe the association for UNC13A and survival in FTD. We included 626 patients with FTD from Dutch memory clinics, including a subcohort of 150 patients with TDP-43 pathology. Survival analyses were performed using Cox proportional hazard models in a recessive manner. Homozygosity for rs12608932-C in UNC13A was associated with a shorter survival compared with other genotypes (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.02–1.60, p = 0.033), which has implications for patient counselling and trial design. ANN NEUROL 2025;97:1062–1066.

AB - UNC13A (rs12608932-CC) is associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and shortens survival in ALS. We aim to describe the association for UNC13A and survival in FTD. We included 626 patients with FTD from Dutch memory clinics, including a subcohort of 150 patients with TDP-43 pathology. Survival analyses were performed using Cox proportional hazard models in a recessive manner. Homozygosity for rs12608932-C in UNC13A was associated with a shorter survival compared with other genotypes (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.02–1.60, p = 0.033), which has implications for patient counselling and trial design. ANN NEUROL 2025;97:1062–1066.

UR - https://www.scopus.com/pages/publications/105002214591

U2 - 10.1002/ana.27245

DO - 10.1002/ana.27245

M3 - Article

C2 - 40214138

AN - SCOPUS:105002214591

SN - 0364-5134

VL - 97

SP - 1062

EP - 1066

JO - Annals of Neurology

JF - Annals of Neurology

IS - 6

ER -

UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia

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