Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults

Thomas W. Buford; Todd M. Manini; John A. Kairalla; Mary M. McDermott; Carlos A. Vaz Fragoso; Haiying Chen; Roger A. Fielding; Abby C. King; Anne B. Newman; Gregory J. Tranah

doi:10.1161/JAHA.118.010009

Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults

Thomas W. Buford, Todd M. Manini, John A. Kairalla, Mary M. McDermott, Carlos A. Vaz Fragoso, Haiying Chen, Roger A. Fielding, Abby C. King, Anne B. Newman, Gregory J. Tranah

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11 Scopus citations

Abstract

Background-—Age-related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome. Methods and Results-—Mitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta-analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta-analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t-RNA-thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P’s<0.0004) were observed. Significant pooled effects on SBP were observed across all transfer RNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined. Conclusions-—These results suggest that mtDNA-encoded variants are associated with variation in SBP and mean arterial pressure among older adults. These results may help identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.

Original language	English
Article number	e010009
Journal	Journal of the American Heart Association
Volume	7
Issue number	18
DOIs	https://doi.org/10.1161/JAHA.118.010009
State	Published - 1 Sep 2018
Externally published	Yes

Keywords

Aging
Blood pressure
DNA sequencing
Mitochondria

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10.1161/JAHA.118.010009

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Buford, T. W., Manini, T. M., Kairalla, J. A., McDermott, M. M., Vaz Fragoso, C. A., Chen, H., Fielding, R. A., King, A. C., Newman, A. B., & Tranah, G. J. (2018). Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults. Journal of the American Heart Association, 7(18), Article e010009. https://doi.org/10.1161/JAHA.118.010009

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title = "Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults",

abstract = "Background-—Age-related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome. Methods and Results-—Mitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta-analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta-analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t-RNA-thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P{\textquoteright}s<0.0004) were observed. Significant pooled effects on SBP were observed across all transfer RNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined. Conclusions-—These results suggest that mtDNA-encoded variants are associated with variation in SBP and mean arterial pressure among older adults. These results may help identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.",

keywords = "Aging, Blood pressure, DNA sequencing, Mitochondria",

author = "Buford, {Thomas W.} and Manini, {Todd M.} and Kairalla, {John A.} and McDermott, {Mary M.} and {Vaz Fragoso}, {Carlos A.} and Haiying Chen and Fielding, {Roger A.} and King, {Abby C.} and Newman, {Anne B.} and Tranah, {Gregory J.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors.",

year = "2018",

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doi = "10.1161/JAHA.118.010009",

language = "English",

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T1 - Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults

AU - Buford, Thomas W.

AU - Manini, Todd M.

AU - Kairalla, John A.

AU - McDermott, Mary M.

AU - Vaz Fragoso, Carlos A.

AU - Chen, Haiying

AU - Fielding, Roger A.

AU - King, Abby C.

AU - Newman, Anne B.

AU - Tranah, Gregory J.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background-—Age-related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome. Methods and Results-—Mitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta-analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta-analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t-RNA-thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P’s<0.0004) were observed. Significant pooled effects on SBP were observed across all transfer RNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined. Conclusions-—These results suggest that mtDNA-encoded variants are associated with variation in SBP and mean arterial pressure among older adults. These results may help identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.

AB - Background-—Age-related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age-related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome. Methods and Results-—Mitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta-analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta-analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t-RNA-thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P’s<0.0004) were observed. Significant pooled effects on SBP were observed across all transfer RNA regions (P=0.0056) in white participants. The individual and aggregate variant results are statistically significant after multiple comparisons adjustment for the number of mtDNA variants and mitochondrial regions examined. Conclusions-—These results suggest that mtDNA-encoded variants are associated with variation in SBP and mean arterial pressure among older adults. These results may help identify mitochondrial activities to explain differences in blood pressure in older adults and generate new hypotheses surrounding mtDNA variation and the regulation of blood pressure.

KW - Aging

KW - Blood pressure

KW - DNA sequencing

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Mitochondrial DNA sequence variants associated with blood pressure among 2 cohorts of older adults

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Keywords

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