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. 2020 Mar:87:138.e7-138.e14.
doi: 10.1016/j.neurobiolaging.2019.09.007. Epub 2019 Sep 24.

Mitonuclear interactions influence Alzheimer's disease risk

Shea J Andrews  1 , Brian Fulton-Howard  1 , Christopher Patterson  2 , G Peggy McFall  3 , Alden Gross  4 , Elias K Michaelis  5 , Alison Goate  1 , Russell H Swerdlow  6 , Judy Pa  7 ; Alzheimer's Disease Neuroimaging Initiative
Affiliations

Mitonuclear interactions influence Alzheimer's disease risk

Shea J Andrews et al. Neurobiol Aging. 2020 Mar.

Abstract

We examined the associations between mitochondrial DNA haplogroups (MT-hgs; mitochondrial haplotype groups defined by a specific combination of single nucleotide polymorphisms labeled as letters running from A to Z) and their interactions with a polygenic risk score composed of nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset (AOO) of dementia. MT-hg K (Odds ratio [OR]: 2.03 [95% CI: 1.04, 3.97]) and a 1 SD larger nMT-PRS (OR: 2.2 [95% CI: 1.68, 2.86]) were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K (OR: 0.45 [95% CI: 0.22, 0.9]) and MT-hg T (OR: 0.22 [95% CI: 0.1, 0.49]) were observed. Individual MT-hgs were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T (Hazard ratio: 0.62 [95% CI: 0.42, 0.91]) and a synergistic interaction between the nMT-PRS and MT-hg V (Hazard ratio: 2.28 [95% CI: 1.19, 4.35]). These results suggest that MT-hgs influence dementia risk and that variants in the nuclear and mitochondrial genome interact to influence the AOO of dementia.

Keywords: Alzheimer's disease; Mitochondria; Polygenic risk score.

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