Association of mitochondrial variants and haplogroups identified by whole exome sequencing with Alzheimer's disease.

ABSTRACT:

Introduction

Findings regarding the association between mitochondrial DNA (mtDNA) variants and Alzheimer's disease (AD) are inconsistent.

Methods

We developed a pipeline for accurate assembly and variant calling in mitochondrial genomes embedded within whole exome sequences (WES) from 10,831 participants from the Alzheimer's Disease Sequencing Project (ADSP). Association of AD risk was evaluated with each mtDNA variant and variants located in 1158 nuclear genes related to mitochondrial function using the SCORE test. Gene-based tests were performed using SKAT-O.

Results

Analysis of 4220 mtDNA variants revealed study-wide significant association of AD with a rare MT-ND4L variant (rs28709356 C>T; minor allele frequency = 0.002; P = 7.3 × 10^-5 ) as well as with

SUBMITTER: Zhang X 

PROVIDER: S-EPMC8764625 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature