GENOMIC SCAN FOR EXERCISE STROKE VOLUME AND CARDIAC OUTPUT IN THE HERITAGE FAMILY STUDY

A genome-wide linkage scan was performed to identify genomic regions influencing submaximal exercise cardiac output (Q) and stroke volume (SV) in the sedentary state and their responses to a standardized 20-week endurance training program. A total of 344 polymorphic markers were used and 292 pairs of siblings from 99 White nuclear families and 90 sibling pairs from 105 Black family units were available for the study. All subjects were healthy but sedentary at baseline. Two exercise tests at 50W were done before and after the training program, and Q and SV (Q50 and SV50, resp.) were measured twice during each test. Baseline phenotypes were adjusted for age, sex and body surface area (BSA). Training responses (post-training û baseline, Δ) were adjusted for age, sex, baseline BSA and baseline value of the phenotype. Linkage analysis was performed using a multipoint variance components model, as implemented in SEGPATH. In Whites, two chromosomal regions showed suggestive linkages with baseline SV50 (7q35-q36, 14q24.3-q31) and two QTLs were detected for baseline Q50 (14q21-q23, 17p13-p12). Both ΔSV50 and ΔQ50 showed suggestive linkage with markers at 2q31 (LODs 1.40 and 1.56, p-values 0.0056 and 0.0037, respectively). An additional QTL for ΔQ50 was detected at chromosome 20q13.2-q13.3 (LOD = 1.50, p = 0.0042). In Blacks, QTLs at 1p22-p13, 3q13, 10p15-p13 and 16q12-q21 were detected for baseline SV50 (LODs from 1.27 to 1.65, p-values from 0.0078 to 0.0029). Baseline Q50 showed linkages with markers at 10p15-p13 (LOD = 1.18, p = 0.010) and 13q11-q12.1 (LOD = 1.20, p = 0.0094). All QTLs include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies. Supported by multiple grants from NIH-NHLBI