A Quantitative Trait Locus For Maximal Exercise Heart Rate On Chromosome 10p13

PURPOSE A genome-wide linkage scan was performed to identify genes affecting maximal heart rate (HRmax) and heart rate reserve (HRrsv) in the sedentary state and their responses to a standardized 20–week endurance training program. METHODS A total of 654 polymorphic markers were used and 353 pairs of siblings from 99 White nuclear families and 102 sibling pairs from 114 Black family units were available. HR was measured by ECG at rest and during maximal exercise and HRrsv was calculated as HRmax - resting HR. Baseline phenotypes were adjusted for age, sex and body mass index, and the training responses (post-training - baseline) were adjusted for age, sex, baseline BMI and baseline value of the response phenotype. Multi-point linkage analyses were done using both regression and variance components-based methods. RESULTS In Whites, baseline HRmax showed the strongest evidence of linkage (LOD=2.54, p=0.0003) with markers on chromosome 10p13. The maximum linkage was detected at 9.4 Mb from pter and a 1-LOD region covered about 7.2 Mb. HRrsv training response QTLs were detected on chromosomes 8q22-q23 (LOD=2.24, p=0.00065 at 107 Mb) and 20q13.1 (LOD=2.51, p=0.00034 at 43.9 Mb). In Blacks, strong evidence of linkage was found for baseline HRrsv on chromosome 7q35 (LOD=3.03, p=0.00009 at 143.2 Mb). CONCLUSIONS All these chromosomal regions include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies.