Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study

Abstract

. Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study. Physiol Genomics 10: 57-62, 2002. First published June 5, 2002 10.1152/physiolgenomics.00043.2002A genome-wide linkage scan was performed for genes affecting submaximal exercise cardiac output (Q) and stroke volume (SV) in the sedentary state and their responses to a standardized 20-wk endurance training program. A total of 509 polymorphic markers were used, and 328 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available. Q and SV were measured in relative steady state during exercise at 50 W (Q50 and SV50, respectively). Baseline phenotypes were adjusted for age, sex, and body surface area (BSA), and the training responses (post-training Ϫ baseline, ⌬) were adjusted for age, sex, baseline BSA, and baseline value of the phenotype. Three analytical strategies were used: a multipoint variance components linkage analysis using all the family data, and regression-based single-and multipoint linkage analyses using pairs of siblings. In whites, baseline SV50 and ⌬SV50 showed promising linkages (P Ͻ 0.0023) with markers on chromosomes 14q31.1 and 10p11.2, respectively. Suggestive evidence of linkage (0.01 Ͼ P Ͼ 0.0023) for ⌬SV50 and ⌬Q50 was detected on chromosome 2q31.1 and for baseline SV50 and Q50 on chromosome 9q32-q33. In blacks, markers on 18q11.2 showed promising linkages with baseline Q50. Suggestive evidence of linkage was found in three regions for baseline SV50 (1p21.3, 3q13.3, 12q13.2) and one for baseline SV50 and Q50 (10p14). All these chromosomal regions include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies. genomic scan; exercise training; linkage analysis THE COMPLETION of the Human Genome Project holds great promise for the development of new insights into biological mechanisms contributing to interindividual differences in responsiveness to acute exercise and exercise training. It has been reported that genetic factors account for a significant proportion of variability in exercise-related phenotypes, such as maximal oxygen uptake (VO 2 max ) and exercise blood pressure, both in the sedentary state and in response to endurance training (2, 4-6). Identification of the genes and mutations responsible for these genetic effects would lead to a better understanding of the biology of adaptation to exercise and, ultimately, enable individualized prescription of exercise training for performance enhancement and for prevention and treatment of several public health problems.Exercise-related phenotypes are typically multifactorial, i.e., they are affected by both environmental and genetic factors. The genetic effect is usually polygenic, i.e., it is determined by a combination of several individual genes, each having a small to moderate effect. Moreover, potential gene-gene and gene-environment interactions further complicate the dissection of the phenotypic variance. Genome-wide linkag...

Genome-Wide Linkage Scan for Physical Activity Levels in the Quebec Family Study

“…However, no such correspondence was found. We have previously reported several QTL for endurance traininginduced changes in maximal oxygen uptake (4), submaximal exercise blood pressure (29) and stroke volume (30), and body composition (7) in the HERITAGE Family study. Comparison with the results of the present study reveals that physical inactivity QTL on chromosome 2p22-p23 does not really coincide with any of the training response QTL, although linkages with stroke volume and maximal oxygen uptake changes were detected with markers about 15 cM upstream and downstream, respectively, of the inactivity QTL.…”

Genomics and Genetics in the Biology of Adaptation to Exercise

“…QTLs for training-induced changes in submaximal exercise (50 W) SV (ΔSV50) and HR (ΔHR50) were found on chromosomes 10p11 and 2q33.3-q34, respectively (252, 304). The ΔSV50 QTL on 10p11 was narrowed down to a 7 Mb region using dense microsatellite mapping.…”

KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise

“…The strongest signal in the original linkage scan for SV50 training response (⌬SV50) phenotype was identified on chromosome 10p11 (VC LOD ϭ 1.96; Reg LOD ϭ 2.69) (18). In the first stage of the fine mapping process we genotyped six additional microsatellite markers on the target region.…”

“…To identify the chromosomal regions that potentially harbor gene(s) affecting SV50 training response, we performed a genome-wide linkage scan using Ͼ500 microsatellite markers (18). The strongest evidence of linkage in white HERITAGE families was detected on chromosome 10p11.…”