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

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

doi:10.1038/s41598-020-79931-6

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

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

^*Tämän työn vastaava kirjoittaja

Kliinisen kemian yksikkö

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

10 Sitaatiot (Scopus)

28 Lataukset (Pure)

Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	611
Julkaisu	Scientific Reports
Vuosikerta	11
Numero	1
DOI - pysyväislinkit	https://doi.org/10.1038/s41598-020-79931-6
Tila	Julkaistu - 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

This work was supported by personal Grants awarded to JL by the Juhani Aho Foundation, Laboratoriolääke-tieteen edistämissäätiö, the Aarne Koskelo Foundation, and the Finnish Medical Foundation. The Young Finns Study (YFS) has been financially supported by the Academy of Finland: Grants 322098, 286284, 134309 [Eye], 126925, 121584, 124282, 129378 [Salve], 117787 [Gendi], and 41071 [Skidi]; the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (Grant X51001); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Cultural Foundation; the Sigrid Juselius Foundation; the Tampere Tuberculosis Foundation; the Emil Aaltonen Foundation; the Yrjö Jahnsson Foundation; the Signe and Ane Gyllenberg Foundation; the Diabetes Research Foundation of Finnish Diabetes Association; the EU Horizon 2020 program (Grant 755320 for TAXINOMISIS; Grant 848146 for To_Aition); the European Research Council (Grant 742927 for MULTIEPIGEN project); the Tampere University Hospital Supporting Foundation; and the Finnish Society of Clinical Chemistry. The Finnish Cardiovascular Study (FINCAVAS) has been financially supported by the Competitive Research Funding of Tampere University Hospital (Grant 9M048 and 9N035), the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Tampere Tuberculosis Foundation, the EU Horizon 2020 program (Grant 755320 for TAXINOMISIS; Grant 848146 for To_Aition), and the Academy of Finland Grant 322098. In addition, we thank Jari Kaikkonen and Janne Asikainen for their technical assistance.

YK:n kestävän kehityksen tavoitteet

Tämä tuotos edistää seuraavia kestävän kehityksen tavoitteita:

SDG 3 – Hyvä terveys ja hyvinvointi

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10.1038/s41598-020-79931-6Lisenssi: CC BY

s41598-020-79931-6Final published version, 801 KBLisenssi: CC BY

http://urn.fi/URN:NBN:fi:tuni-202105265465Lisenssi: CC BY

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Laaksonen, J., Mishra, P. P., Seppälä, I., Lyytikäinen, L.-P., Raitoharju, E., Mononen, N., Lepistö, M., Almusa, H., Ellonen, P., Hutri-Kähönen, N., Juonala, M., Raitakari, O., Kähönen, M., Salonen, J. T., & Lehtimäki, T. (2021). Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts. Scientific Reports, 11(1), Artikkeli 611. https://doi.org/10.1038/s41598-020-79931-6

@article{d3c3b58f50374c56b41da5f94e2fbe5c,

title = "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.",

author = "Jaakko Laaksonen and Mishra, \{Pashupati P.\} and Ilkka Sepp{\"a}l{\"a} and Leo-Pekka Lyytik{\"a}inen and Emma Raitoharju and Nina Mononen and Maija Lepist{\"o} and Henrikki Almusa and Pekka Ellonen and Nina Hutri-K{\"a}h{\"o}nen and Markus Juonala and Olli Raitakari and Mika K{\"a}h{\"o}nen and Salonen, \{Jukka T.\} and Terho Lehtim{\"a}ki",

note = "Funding Information: This work was supported by personal Grants awarded to JL by the Juhani Aho Foundation, Laboratoriol{\"a}{\"a}ke-tieteen edist{\"a}miss{\"a}{\"a}ti{\"o}, the Aarne Koskelo Foundation, and the Finnish Medical Foundation. The Young Finns Study (YFS) has been financially supported by the Academy of Finland: Grants 322098, 286284, 134309 [Eye], 126925, 121584, 124282, 129378 [Salve], 117787 [Gendi], and 41071 [Skidi]; the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (Grant X51001); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Cultural Foundation; the Sigrid Juselius Foundation; the Tampere Tuberculosis Foundation; the Emil Aaltonen Foundation; the Yrj{\"o} Jahnsson Foundation; the Signe and Ane Gyllenberg Foundation; the Diabetes Research Foundation of Finnish Diabetes Association; the EU Horizon 2020 program (Grant 755320 for TAXINOMISIS; Grant 848146 for To\_Aition); the European Research Council (Grant 742927 for MULTIEPIGEN project); the Tampere University Hospital Supporting Foundation; and the Finnish Society of Clinical Chemistry. The Finnish Cardiovascular Study (FINCAVAS) has been financially supported by the Competitive Research Funding of Tampere University Hospital (Grant 9M048 and 9N035), the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Tampere Tuberculosis Foundation, the EU Horizon 2020 program (Grant 755320 for TAXINOMISIS; Grant 848146 for To\_Aition), and the Academy of Finland Grant 322098. In addition, we thank Jari Kaikkonen and Janne Asikainen for their technical assistance. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

doi = "10.1038/s41598-020-79931-6",

language = "English",

volume = "11",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

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Laaksonen, J, Mishra, PP, Seppälä, I, Lyytikäinen, L-P , Raitoharju, E , Mononen, N, Lepistö, M, Almusa, H, Ellonen, P, Hutri-Kähönen, N, Juonala, M, Raitakari, O, Kähönen, M, Salonen, JT & Lehtimäki, T 2021, 'Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts', Scientific Reports, Vuosikerta 11, Nro 1, 611. https://doi.org/10.1038/s41598-020-79931-6

TY - JOUR

T1 - Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts

AU - Laaksonen, Jaakko

AU - Mishra, Pashupati P.

AU - Seppälä, Ilkka

AU - Lyytikäinen, Leo-Pekka

AU - Raitoharju, Emma

AU - Mononen, Nina

AU - Lepistö, Maija

AU - Almusa, Henrikki

AU - Ellonen, Pekka

AU - Hutri-Kähönen, Nina

AU - Juonala, Markus

AU - Raitakari, Olli

AU - Kähönen, Mika

AU - Salonen, Jukka T.

AU - Lehtimäki, Terho

N1 - Funding Information: This work was supported by personal Grants awarded to JL by the Juhani Aho Foundation, Laboratoriolääke-tieteen edistämissäätiö, the Aarne Koskelo Foundation, and the Finnish Medical Foundation. The Young Finns Study (YFS) has been financially supported by the Academy of Finland: Grants 322098, 286284, 134309 [Eye], 126925, 121584, 124282, 129378 [Salve], 117787 [Gendi], and 41071 [Skidi]; the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (Grant X51001); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Cultural Foundation; the Sigrid Juselius Foundation; the Tampere Tuberculosis Foundation; the Emil Aaltonen Foundation; the Yrjö Jahnsson Foundation; the Signe and Ane Gyllenberg Foundation; the Diabetes Research Foundation of Finnish Diabetes Association; the EU Horizon 2020 program (Grant 755320 for TAXINOMISIS; Grant 848146 for To_Aition); the European Research Council (Grant 742927 for MULTIEPIGEN project); the Tampere University Hospital Supporting Foundation; and the Finnish Society of Clinical Chemistry. The Finnish Cardiovascular Study (FINCAVAS) has been financially supported by the Competitive Research Funding of Tampere University Hospital (Grant 9M048 and 9N035), the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Tampere Tuberculosis Foundation, the EU Horizon 2020 program (Grant 755320 for TAXINOMISIS; Grant 848146 for To_Aition), and the Academy of Finland Grant 322098. In addition, we thank Jari Kaikkonen and Janne Asikainen for their technical assistance. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-020-79931-6

DO - 10.1038/s41598-020-79931-6

M3 - Article

AN - SCOPUS:85099209578

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 611

ER -

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

Abstrakti

Rahoitus

YK:n kestävän kehityksen tavoitteet

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

Pääsy asiakirjaan

Sormenjälki

Siteeraa tätä