Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality

Balewgizie S. Tegegne; M. Abdullah Said; Alireza Ani; Arie M. van Roon; Sonia Shah; Eco J.C. de Geus; Pim van der Harst; Harriëtte Riese; Ilja M. Nolte; Harold Snieder

doi:10.1038/s42003-023-05376-y

Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality

Balewgizie S. Tegegne, M. Abdullah Said, Alireza Ani, Arie M. van Roon, Sonia Shah, Eco J.C. de Geus, Pim van der Harst, Harriëtte Riese, Ilja M. Nolte, Harold Snieder^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously. In a prospective phenotypic relationship between HRV and mortality during a median follow-up of seven years, individuals with lower HRV had higher risk of dying from any cause. Genetically predicted HRV, as determined by the genetic risk scores, was not associated with mortality. To the best of our knowledge, the findings provide novel biological insights into the mechanisms underlying HRV. These results also underline the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.

Original language	English
Article number	1013
Pages (from-to)	1-10
Number of pages	10
Journal	Communications biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05376-y
Publication status	Published - 6 Oct 2023

Bibliographical note

Funding Information:
The study was carried out using the UK Biobank Resource under Application Number 12006. We thank the Center for Information Technology of the University of Groningen for their support and for providing access to the Peregrine high-performance computing cluster. B.S. Tegegne is supported by a scholarship from the Graduate School of Medical Science, University of Groningen, the Netherlands.

Funding Information:
The study was carried out using the UK Biobank Resource under Application Number 12006. We thank the Center for Information Technology of the University of Groningen for their support and for providing access to the Peregrine high-performance computing cluster. B.S. Tegegne is supported by a scholarship from the Graduate School of Medical Science, University of Groningen, the Netherlands.

Publisher Copyright:
© 2023, Springer Nature Limited.

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@article{897c1dcba2d743bc9bbbc8fd36e811e6,

title = "Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality",

abstract = "Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously. In a prospective phenotypic relationship between HRV and mortality during a median follow-up of seven years, individuals with lower HRV had higher risk of dying from any cause. Genetically predicted HRV, as determined by the genetic risk scores, was not associated with mortality. To the best of our knowledge, the findings provide novel biological insights into the mechanisms underlying HRV. These results also underline the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.",

author = "Tegegne, {Balewgizie S.} and Said, {M. Abdullah} and Alireza Ani and {van Roon}, {Arie M.} and Sonia Shah and {de Geus}, {Eco J.C.} and {van der Harst}, Pim and Harri{\"e}tte Riese and Nolte, {Ilja M.} and Harold Snieder",

note = "Funding Information: The study was carried out using the UK Biobank Resource under Application Number 12006. We thank the Center for Information Technology of the University of Groningen for their support and for providing access to the Peregrine high-performance computing cluster. B.S. Tegegne is supported by a scholarship from the Graduate School of Medical Science, University of Groningen, the Netherlands. Funding Information: The study was carried out using the UK Biobank Resource under Application Number 12006. We thank the Center for Information Technology of the University of Groningen for their support and for providing access to the Peregrine high-performance computing cluster. B.S. Tegegne is supported by a scholarship from the Graduate School of Medical Science, University of Groningen, the Netherlands. Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",

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AU - Tegegne, Balewgizie S.

AU - Said, M. Abdullah

AU - Ani, Alireza

AU - van Roon, Arie M.

AU - Shah, Sonia

AU - de Geus, Eco J.C.

AU - van der Harst, Pim

AU - Riese, Harriëtte

AU - Nolte, Ilja M.

AU - Snieder, Harold

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PY - 2023/10/6

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N2 - Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously. In a prospective phenotypic relationship between HRV and mortality during a median follow-up of seven years, individuals with lower HRV had higher risk of dying from any cause. Genetically predicted HRV, as determined by the genetic risk scores, was not associated with mortality. To the best of our knowledge, the findings provide novel biological insights into the mechanisms underlying HRV. These results also underline the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.

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ER -

Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality

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