Genome-wide association studies of TDP-43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B.

ABSTRACT:

Introduction

Transactive response DNA binding protein 43 kDa (TDP-43) proteinopathy has been linked to cognitive decline and often co-occurs with hippocampal sclerosis (HS). To identify genetic markers of TDP-43 proteinopathy and HS, we performed genome-wide association studies (GWASs) of HS and TDP-43 inclusions.

Methods

Genetic data were obtained through the Alzheimer Disease Genetics Consortium and collaborating sites (HS: N = 9509; TDP-43: N = 4669). Statistical analyses included association analysis with HS and TDP-43 inclusions and meta-analysis, a mediation analysis, and fine mapping of the transmembrane protein 106B (TMEM106B) region.

Results

Two regions achieved genome-wide significance with TDP-43: apolipoprotein E (APOE) and TMEM106B. Three loci reached gen

SUBMITTER: Godrich D 

PROVIDER: S-EPMC12598407 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature