Overview of the HERITAGE Family Study

The aim of the HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study was to investigate the magnitude of the individual differences in response to a standardized endurance exercise program, the importance of familial aggregation, and the genetics of the response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors.

Figure 1. Model integrating the various components of HERITAGE. Subjects were measured in the sedentary state and after the exercise program intervention. Cardiorespiratory fitness, exercise hemodynamics, and subsets of cardiometabolic and diabetic risk factors were monitored. Differences between Blacks and Whites were investigated. Studies on genetic and non-genetic determinants of human variability in the sedentary state and in response to endurance exercise training were pursued.

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The HERITAGE Family Study was funded by National Heart, Lung, and Blood Institute grants HL-45670, HL-47323, HL-47317, HL-47327, and HL-47321

Phase 1 of HERITAGE (1992 to 1997) was devoted to the recruitment of White and Black families and to extensive testing of all individuals before and after a 20-week laboratory-controlled and fully standardized exercise program. Five centers were involved: University of Minnesota (PI: Arthur Leon), University of Arizona and then University of Indiana (PI: James Skinner), University of Texas at Austin (PI: Jack Wilmore), Washington University (PI: D.C. Rao), and Laval University in Quebec City (PI: Claude Bouchard). Washington University served as the Data Coordinating Center (PI: Rao). Claude Bouchard, leader of the project, served as the chair of the HERITAGE Steering Committee and as the coordinator of the core facilities (lipid core, steroid core, hormone core, cell lines core) located at Laval University in Quebec City.

In Phase 2 (1997 to 2001), the HERITAGE database was used extensively to document the range of human variation in the response to regular exercise, level of familial aggregation and heritability, and differences in response by age, gender, and race. A panel of pre-selected markers in candidate genes was used to investigate possible associations with the baseline and response levels for a variety of phenotypes. A first genome-wide scan with a panel of about 300 markers was undertaken for several baseline and response phenotypes.

Phase 3 (2001 to 2005) dealt with the genetic epidemiology of training-induced changes in major cardiovascular disease risk factors, with an emphasis on possible Black and White differences. Targeted cardiovascular disease and type 2 diabetes risk factors and their responses to regular exercise were investigated, with an emphasis on Black and White differences. Microarray studies of vastus lateralis skeletal muscle mRNA obtained in a subset of 78 HERITAGE participants have been undertaken, with the goal of comparing the profile of those who did not improve and those who almost doubled their insulin sensitivity in response to regular exercise. More refined genome-wide linkage scans were completed by the end of Phase 3 with a denser panel of markers (650 microsatellites) and more powerful analytical strategies.

Phase 4 (2006 to 2013) focused on genome-wide association explorations of the response to regular exercise of cardiorespiratory fitness and several metabolic traits.