A 3'UTR Insertion Is a Candidate Causal Variant at the <i>TMEM106B</i> Locus Associated with Increased Risk for FTLD-TDP.

ABSTRACT:

Background and objectives

Single nucleotide variants near TMEM106B associate with risk of frontotemporal lobar dementia with TDP-43 inclusions (FTLD-TDP) and Alzheimer's disease (AD) in genome-wide association studies (GWAS), but the causal variant at this locus remains unclear. Here we asked whether a novel structural variant on TMEM106B is the causal variant.

Methods

An exploratory analysis identified structural variants on neurodegeneration-related genes. Subsequent analyses focused on an Alu element insertion on the 3'UTR of TMEM106B. This study included data from longitudinal aging and neurogenerative disease cohorts at Stanford University, case-control cohorts in the Alzheimer's Disease Sequencing Project (ADSP), and expression and proteomic

SUBMITTER: Chemparathy A 

PROVIDER: S-EPMC10350161 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature