Abstract
Elevated heart rate has been proposed as an independent risk factor for cardiovascular diseases, but their interrelationships are not well understood. In this study, we performed a genome-wide linkage scan in 1,026 individuals (mean age 30.6 years, 54.5% women) from 73 extended families of Mongolia and determined quantitative trait loci that influence heart rate. The DNA samples were genotyped using deCODE 1,039 microsatellite markers for 3 cM density genome-wide linkage scan. Correlation analysis was carried out to evaluate the correlation of the covariates and the heart rate. T-tests of the heart rate were also performed on sex, smoking and alcohol intake. Consequently, this model was used in a nonparametric genome-wide linkage analysis using variance component model to create a multipoint logarithm of odds (LOD) score and a corresponding P value. In the adjusted model, the heritability of heart rate was estimated as 0.32 (P<.0001) and a maximum multipoint LOD score of 2.03 was observed in 77 cM region at chromosome 18. The second largest LOD score of 1.52 was seen on chromosome 5 at 216 cM. Genes located on the specified locations in chromosomes 5 and 18 may be involved in the regulation of heart rate.
Highlights
Epidemiological and clinical studies suggest that elevated heart rate is a potential risk factor for a variety of cardiovascular diseases (CVD) including atherosclerosis, coronary artery disease (CAD), myocardial infarction, arterial hypertension and heart failure (Greenland et al, 1999; Colhoun et al, 2001; King et al, 2006; Palatini et al, 2006; Brasel et al, 2007; Fox et al, 2007; Rogowski et al, 2007)
The data set of examined individuals included a large number of relative pair types as we have recruited extended families
They pointed out that genetic components may play an essential role in the regulation of heart rate variability
Summary
Epidemiological and clinical studies suggest that elevated heart rate is a potential risk factor for a variety of cardiovascular diseases (CVD) including atherosclerosis, coronary artery disease (CAD), myocardial infarction, arterial hypertension and heart failure (Greenland et al, 1999; Colhoun et al, 2001; King et al, 2006; Palatini et al, 2006; Brasel et al, 2007; Fox et al, 2007; Rogowski et al, 2007). A number of twin and family studies have reported that genetic factors influence the regulation of heart rate (Singh et al, 1999; Woodman et al, 2002; Wilk et al, 2002; Martin et al, 2004; Neumann et al, 2005; Laramie et al, 2006; Larson et al, 2007; Newton-Cheh et al, 2007; O'Donnell et al, 2007). Singh et al, (2002) identified significant genetic regions contributing to heart rate variability on chromosome 15 at 62 cM and chromosome 2 at 153 cM. Wilk et al (2002) identified that 195.06 cM region of chromosome 4 is seemingly related to the variability in resting heart rate In the recent meta-analysis of genome-wide scans for study networks that enrolled Caucasians and AfricanAmericans, Laramie et al (2006) concluded in the replication between various ethnic groups as well as the study networks with low heterogeneity on chromosome 5p13-14. Wilk et al (2002) identified that 195.06 cM region of chromosome 4 is seemingly related to the variability in resting heart rate
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