Structural variation detection and association analysis of whole-genome-sequence data from 16,543 Alzheimer's disease sequencing project subjects.

ABSTRACT:

Introduction

The role of structural variations (SVs) in Alzheimer's disease (AD) remains understudied.

Methods

We analyzed whole-genome sequencing data from the Alzheimer's Disease Sequencing Project (N = 16,543) and identified 400,234 (168,223 high-quality) SVs. Laboratory validation yielded a sensitivity of 82% (85% for high-quality).

Results

We found a burden of singletons (odds ratio [OR] = 1.07, p = 0.0017) and homozygous deletions (OR = 1.14, p < 0.0001) in cases. On AD genes, we observed the ultra-rare SVs associated with the disease, including protein-altering SVs in ABCA7, APP, PLCG2, and SORL1. Twenty-one SVs are in linkage disequilibrium (LD) with known AD-risk variants, exemplified by a 5k deletion in LD (R² = 0.99) with rs143080277 in NCK2. We

SUBMITTER: Wang H 

PROVIDER: S-EPMC12173831 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature