Assembly of 809 whole mitochondrial genomes with clinical, imaging, and fluid biomarker phenotyping

Abstract

Introduction Mitochondrial genetics are an important but largely neglected area of research in Alzheimer’s disease. A major impediment is the lack of data sets. Methods We used an innovative, rigorous approach, combining several existing tools with our own, to accurately assemble and call variants in 809 whole mitochondrial genomes. Results To help address this impediment, we prepared a data set that consists of 809 complete and annotated mitochondrial genomes with samples from the Alzheimer’s Disease Neuroimaging Initiative. These whole mitochondrial genomes include rich phenotyping, such as clinical, fluid biomarker, and imaging data, all of which is available through the Alzheimer’s Disease Neuroimaging Initiative website. Genomes are cleaned, annotated, and prepared for analysis. Discussion These data provide an important resource for investigating the impact of mitochondrial genetic variation on risk for Alzheimer’s disease and other phenotypes that have been measured in the Alzheimer’s Disease Neuroimaging Initiative samples.

Exploratory analysis of mtDNA haplogroups in two Alzheimer's longitudinal cohorts

“…Ridge et al. recently published haplogroup assignments for 809 ADNI participants with complete mtDNA sequences 37 . Participants were clinically characterized by initial diagnosis, which included 191 AD and 279 CN individuals.…”

“…Only ADNI participants with an available complete mtDNA sequence were used in the present study. This subset of ADNI participants have undergone complete mtDNA sequencing and those sequences were used to assign mtDNA haplogroups 37 . There was no overlap between KUADC and ADNI subjects in this study.…”

Mitonuclear interactions influence Alzheimer's disease risk

“…Additional mitochondrial genetic variants were made available via imputation of the mitochondrial genome, as previously described ( McInerney et al, 2019 ), using a custom reference panel of mitochondrial genome sequences and the chromosome X imputation protocol in IMPUTE2 ( Howie et al, 2009 ). An additional 809 samples with mitochondrial variants were made available via whole genome sequencing ( Ridge et al, 2018 ). MT-hgs were assigned to the genotyped/imputed data set (SNPs with an info score >0.4) using HaploGrep2 ( Weissensteiner et al, 2016 ), whereas in the whole genome sequenced data set, MT-hgs were assigned using Phy-Mer ( Navarro-Gomez et al, 2015 ).…”

The Other Side of Alzheimer’s Disease: Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers

“…However, these results still need to be confirmed. Finally, giving the importance of mitochondria in AD pathogenesis, Ridge et al recently created a new extended dataset of mitochondrial genomes to investigate the impact of mitochondrial genetic variation on the risk for AD, with the aim of helping further research on mitochondrial peripheral biomarkers [176].…”