Identifying Genetic Variants for Heart Rate Variability in the Acetylcholine Pathway

Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. 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, S...

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Vydáno v:	PloS one Ročník 9; číslo 11; s. e112476
Hlavní autoři:	Riese, Harriëtte, Muñoz, Loretto M., Hartman, Catharina A., Ding, Xiuhua, Su, Shaoyong, Oldehinkel, Albertine J., van Roon, Arie M., van der Most, Peter J., Lefrandt, 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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 10.11.2014 Public Library of Science (PLoS)
Témata:	Acetylcholine Acetylcholine - metabolism Acetylcholinesterase Adolescent Adult Analysis Biology and Life Sciences Cardiology Cardiovascular diseases Cardiovascular Diseases - genetics Cardiovascular Diseases - metabolism Child Cohort Studies Epidemiology European Continental Ancestry Group - genetics Female Genes Genetic Association Studies Genetic diversity Genetic variance Genome-wide association studies Genomes Genomics Health aspects Health psychology Health risks Heart rate Heart Rate - genetics Humans Hypertension Interdisciplinary aspects Male Medicine Medicine and Health Sciences Meta-analysis Middle Aged Mortality Nervous system Outdoor air quality Parasympathetic nervous system Pediatrics Polymorphism, Single Nucleotide Psychiatry Psychopathology Risk factors Signal Transduction Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Twins Variability Young Adult United States > US Netherlands Georgia
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. 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 established measure 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 and most 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: HR CAH AJO RTG PVDH DIB GW BWJHP EJCDG XW HS. Performed the experiments: HR XD SS AMVR JL NV CMML JJH GW EJCDG. Analyzed the data: LMM XD SS IMN PJVDM XW. Wrote the paper: HR LMM CAH XD SS AJO AMVR IMN PJVDM JL RTG PVDH NV CMML DIB JJH GW BWJHP EJCDG XW HS. Competing Interests: The authors have declared that no competing interests exist. These authors are shared last authors on this work.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0112476