Identifying genetic variants for heart rate variability in the acetylcholine pathway

Harriëtte Riese, Loretto M. Muñoz, Catharina A. Hartman, Xiuhua Ding, Shaoyong Su, Albertine J. Oldehinkel, Arie M. Van Roon, Peter J. Van Der Most, Joop Lefrt, Ron T. Gansevoort, Pim Van Der Harst, Niek Verweij, Carmilla M.M. Licht, Dorret I. Boomsma, Jouke Jan Hottenga, Gonneke Willemsen, Brenda W.J.H. Penninx, Ilja M. Nolte, Eco J.C. De Geus, Xiaoling Wang & 1 others Harold Snieder

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Heart rate variability is an important risk factor for cardiovascular disease and all-causemortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an establishedmeasure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a two stage design in individuals of European descent. First, analyses were performed in a discovery sample of four cohorts (n = 3429, discovery stage). Second, findings were replicated in three independent cohorts (n = 3311, replication stage), and finally the two stages were combined in a meta-analysis (n = 6740). RMSSD data were obtained under resting conditions. After correction for multiple testing, none of the SNPs showed an association with RMSSD. In conclusion, no common genetic variants for heart rate variability were identified in the largest andmost comprehensive candidate gene study on the acetylcholine pathway to date. Future gene finding efforts for RMSSD may want to focus on hypothesis free approaches such as the genome-wide association study.

Original languageEnglish (US)
Article numbere112476
JournalPloS one
Volume9
Issue number11
DOIs
StatePublished - Nov 10 2014

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acetylcholine
Acetylcholine
heart rate
Heart Rate
Genes
genes
Genome-Wide Association Study
meta-analysis
cardiovascular diseases
Single Nucleotide Polymorphism
Meta-Analysis
Cardiovascular Diseases
risk factors
heart
Testing
testing
sampling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Riese, H., Muñoz, L. M., Hartman, C. A., Ding, X., Su, S., Oldehinkel, A. J., ... Snieder, H. (2014). Identifying genetic variants for heart rate variability in the acetylcholine pathway. PloS one, 9(11), [e112476]. https://doi.org/10.1371/journal.pone.0112476

Identifying genetic variants for heart rate variability in the acetylcholine pathway. / Riese, Harriëtte; Muñoz, Loretto M.; Hartman, Catharina A.; Ding, Xiuhua; Su, Shaoyong; Oldehinkel, Albertine J.; Van Roon, Arie M.; Van Der Most, Peter J.; Lefrt, Joop; Gansevoort, Ron T.; Van Der Harst, Pim; Verweij, Niek; Licht, Carmilla M.M.; Boomsma, Dorret I.; Hottenga, Jouke Jan; Willemsen, Gonneke; Penninx, Brenda W.J.H.; Nolte, Ilja M.; De Geus, Eco J.C.; Wang, Xiaoling; Snieder, Harold.

In: PloS one, Vol. 9, No. 11, e112476, 10.11.2014.

Research output: Contribution to journalArticle

Riese, H, Muñoz, LM, Hartman, CA, Ding, X, Su, S, Oldehinkel, AJ, Van Roon, AM, Van Der Most, PJ, Lefrt, J, Gansevoort, RT, Van Der Harst, P, Verweij, N, Licht, CMM, Boomsma, DI, Hottenga, JJ, Willemsen, G, Penninx, BWJH, Nolte, IM, De Geus, EJC, Wang, X & Snieder, H 2014, 'Identifying genetic variants for heart rate variability in the acetylcholine pathway', PloS one, vol. 9, no. 11, e112476. https://doi.org/10.1371/journal.pone.0112476
Riese, Harriëtte ; Muñoz, Loretto M. ; Hartman, Catharina A. ; Ding, Xiuhua ; Su, Shaoyong ; Oldehinkel, Albertine J. ; Van Roon, Arie M. ; Van Der Most, Peter J. ; Lefrt, Joop ; Gansevoort, Ron T. ; Van Der Harst, Pim ; Verweij, Niek ; Licht, Carmilla M.M. ; Boomsma, Dorret I. ; Hottenga, Jouke Jan ; Willemsen, Gonneke ; Penninx, Brenda W.J.H. ; Nolte, Ilja M. ; De Geus, Eco J.C. ; Wang, Xiaoling ; Snieder, Harold. / Identifying genetic variants for heart rate variability in the acetylcholine pathway. In: PloS one. 2014 ; Vol. 9, No. 11.
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AU - Hartman, Catharina A.

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AU - Su, Shaoyong

AU - Oldehinkel, Albertine J.

AU - Van Roon, Arie M.

AU - Van Der Most, Peter J.

AU - Lefrt, Joop

AU - Gansevoort, Ron T.

AU - Van Der Harst, Pim

AU - Verweij, Niek

AU - Licht, Carmilla M.M.

AU - Boomsma, Dorret I.

AU - Hottenga, Jouke Jan

AU - Willemsen, Gonneke

AU - Penninx, Brenda W.J.H.

AU - Nolte, Ilja M.

AU - De Geus, Eco J.C.

AU - Wang, Xiaoling

AU - Snieder, Harold

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