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...

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Autores principales:	Jaakko Laaksonen, Pashupati P. Mishra, Ilkka Seppälä, Leo-Pekka Lyytikäinen, Emma Raitoharju, Nina Mononen, Maija Lepistö, Henrikki Almusa, Pekka Ellonen, Nina Hutri-Kähönen, Markus Juonala, Olli Raitakari, Mika Kähönen, Jukka T. Salonen, Terho Lehtimäki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d1f4a2fafbc746db82b61c974ee8830e
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spelling	oai:doaj.org-article:d1f4a2fafbc746db82b61c974ee8830e2021-12-02T15:23:10ZExamining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts10.1038/s41598-020-79931-62045-2322https://doaj.org/article/d1f4a2fafbc746db82b61c974ee8830e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79931-6https://doaj.org/toc/2045-2322Abstract 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.Jaakko LaaksonenPashupati P. MishraIlkka SeppäläLeo-Pekka LyytikäinenEmma RaitoharjuNina MononenMaija LepistöHenrikki AlmusaPekka EllonenNina Hutri-KähönenMarkus JuonalaOlli RaitakariMika KähönenJukka T. SalonenTerho LehtimäkiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jaakko Laaksonen Pashupati P. Mishra Ilkka Seppälä Leo-Pekka Lyytikäinen Emma Raitoharju Nina Mononen Maija Lepistö Henrikki Almusa Pekka Ellonen Nina Hutri-Kähönen Markus Juonala Olli Raitakari Mika Kähönen Jukka T. Salonen Terho Lehtimäki Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts
description	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.
format	article
author	Jaakko Laaksonen Pashupati P. Mishra Ilkka Seppälä Leo-Pekka Lyytikäinen Emma Raitoharju Nina Mononen Maija Lepistö Henrikki Almusa Pekka Ellonen Nina Hutri-Kähönen Markus Juonala Olli Raitakari Mika Kähönen Jukka T. Salonen Terho Lehtimäki
author_facet	Jaakko Laaksonen Pashupati P. Mishra Ilkka Seppälä Leo-Pekka Lyytikäinen Emma Raitoharju Nina Mononen Maija Lepistö Henrikki Almusa Pekka Ellonen Nina Hutri-Kähönen Markus Juonala Olli Raitakari Mika Kähönen Jukka T. Salonen Terho Lehtimäki
author_sort	Jaakko Laaksonen
title	Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts
title_short	Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts
title_full	Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts
title_fullStr	Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts
title_full_unstemmed	Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts
title_sort	examining the effect of mitochondrial dna variants on blood pressure in two finnish cohorts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d1f4a2fafbc746db82b61c974ee8830e
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Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts

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