Dataset Information

Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

ABSTRACT: High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension.

SUBMITTER: Laaksonen J

PROVIDER: S-EPMC7804469 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

Laaksonen Jaakko J Mishra Pashupati P PP Seppälä Ilkka I Lyytikäinen Leo-Pekka LP Raitoharju Emma E Mononen Nina N Lepistö Maija M Almusa Henrikki H Ellonen Pekka P Hutri-Kähönen Nina N Juonala Markus M Raitakari Olli O Kähönen Mika M Salonen Jukka T JT Lehtimäki Terho T

Scientific reports 20210112 1

High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular ...[more]

PMID: 33436758

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Project description: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 (mt DNA ) 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 mt DNA 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 mt DNA variants and mitochondrial regions examined. Conclusions These results suggest that mt DNA -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 mt DNA variation and the regulation of blood pressure. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifiers: NCT 01072500 and NCT 00116194.

Dataset Information

Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

Publications

Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

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