Submitted on January 10, 2007
Accepted on October 3, 2007
Genome-wide linkage scan for submaximal exercise heart rate in the HERITAGE Family Study
Nadine Spielmann1, Arthur S. Leon2, DC Rao3, Treva Rice4, James S. Skinner5, Tuomo Rankinen1, and Claude Bouchard1*
1 Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
2 School of Kinesiology, University of Minnesota, Minneapolis, Minnesota, United States
3 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States; Departments of Genetics and Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States
4 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States
5 Kinesiology, Indiana University, Bloomington, Missouri, United States
* To whom correspondence should be addressed. E-mail: bouchac{at}pbrc.edu.
Objective: The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-week endurance training program in Blacks and Whites of the HERITAGE Family Study. Methods/Results: A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 Watts (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (post-training minus baseline, 
) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used: a multipoint variance components and a regression-based multipoint linkage analysis. In Whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD=2.64; p=0.0002) and ) HR60 (LOD=2.10; p=0.0009) and for ) HR50 on chromosome 2q33.3 (LOD=2.13; p=0.0009). In Blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD=2.43, p=0.0004 with D10S597). Conclusion: The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in Whites, on 10q25-26 for baseline HR60 in Blacks and on 18q21-22 for both, baseline HR50 and ) HR60 in Whites.
