# UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia

## TL;DR

A genetic variation in UNC13A is linked to shorter survival in patients with frontotemporal dementia.

## Contribution

This study identifies a specific UNC13A polymorphism as a survival predictor in frontotemporal dementia patients.

## Key findings

- UNC13A rs12608932-CC homozygosity is associated with shorter survival in FTD patients.
- The hazard ratio for survival was 1.28 in UNC13A CC homozygotes compared to other genotypes.
- The finding has implications for patient counseling and clinical trial design in FTD.

## 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