Submitted on August 14, 2007
Accepted on April 14, 2008
THE GENETIC CONTRIBUTION TO HEART RATE AND HEART RATE VARIABILITY IN QUIESCENT MICE
Reuben Howden1*, Eric Liu1, Laura Miller-DeGraff1, Heather L Keener2, Christopher Walker1, James A Clark1, Page H Myers1, Douglas Clay Rouse1, Tim Wiltshire3, and Steven R. Kleeberger4
1 Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Durham, North Carolina, United States
2 Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Durham, Delaware, United States
3 Genomics Institute of the Novartis Research Foundation, San Diego, California, United States
4 National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States
* To whom correspondence should be addressed. E-mail: howden{at}niehs.nih.gov.
Background. Recent studies have suggested a genetic component to heart rate (HR) and heart rate variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Methods and Results. Electrocardiogram (ECG) data were recorded from thirty strains of inbred mice and twenty-nine RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low frequency (LF) and high frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genome-wide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated Heart rate 1, Hr1]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated Heart rate variability high frequency 1, Hrvhf1] and three suggestive QTLs on chromosomes 2, 11 and 15. Conclusions. Results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. Lack of correlation between HR and HRV phenotypes in some inbred strains suggests different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest.
