Mitonuclear interactions influence Alzheimer’s disease risk

Andrews, S. J.; Fulton-Howard, B.; Patterson, C.; McFall, G. P.; Gross, A.; Michaelis, E. K.; Goate, A. M. J.; Swerdlow, R. H.; Pa, J.; the Alzheimers Disease Neuroimaging Initiative,

doi:10.1101/654400

bioRxiv · 10.1101/654400

Mitonuclear interactions influence Alzheimer’s disease risk

Andrews, S. J.·Fulton-Howard, B.·Patterson, C.·McFall, G. P.·Gross, A.·Michaelis, E. K.·Goate, A. M. J.·Swerdlow, R. H.·Pa, J.·the Alzheimers Disease Neuroimaging Initiative,

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Abstract

We examined the associations between mitochondrial DNA haplogroups (MT-hg) and their interactions with a polygenic risk score based on nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset of dementia (AOO). Logistic regression was used to determine the effect of MT-hgs and nMT-PRS on dementia at baseline (332 controls / 204 cases). Cox proportional hazards models were used to model dementia AOO (n=1047; 433 incident cases). Additionally, we tested for interactions between MT-hg and nMT-PRS in the logistic and Cox models. MT-hg K and a one SD larger nMT-PRS were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K and T were observed. Individual MT-hg were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T and a synergistic interaction between the nMT-PRS and MT-hg V. These results suggest that MT-hgs influence dementia risk, and that variants in the nuclear and mitochondrial genome interact to influence the age of onset of dementia.\n\nHighlightsO_LIMitochondrial dysfunction has been proposed to influence dementia risk\nC_LIO_LIMT-hg K and T interacted with a genetic risk score to reduce dementia risk\nC_LIO_LIMT-hg T and V interacted with a genetic risk score to influence dementia age of onset\nC_LI

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Andrews, S. J., Fulton-Howard, B., Patterson, C., McFall, G. P., Gross, A., Michaelis, E. K., Goate, A. M. J., Swerdlow, R. H., Pa, J., the Alzheimers Disease Neuroimaging Initiative,. 2019-05-31. Mitonuclear interactions influence Alzheimer’s disease risk. https://doi.org/10.1101/654400

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