Locus on Chromosome 2q37 Is Associated With Hemodynamic Training Responses: The Heritage Family Study

Endurance training-induced changes in hemodynamic traits are heritable. However, few genes associated with blood pressure training responses have been identified. PURPOSE: To perform a genome-wide association study (GWAS) to uncover DNA sequence variants that are associated with submaximal exercise blood pressure training responses in the HERITAGE Family Study. METHODS: Systolic (SBP50) and diastolic (DBP50) blood pressures were measured during steady-state exercise at 50 W on two separate days both before and after a 20-week endurance training program in 483 white subjects from 99 families. Pulse pressure (PP50) was calculated as the difference between SBP50 and DBP50. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the GWAS analyses, which were done using the MERLIN software package (single-SNP analyses) and standard regression models (multivariate analyses). RESULTS: The strongest associations with age, sex, baseline BMI and baseline trait value-adjusted PP50 (p=4.4×10-9) and SBP50 (p=1.8×10-7) training responses were detected with a cluster of six correlated SNPs (pairwise r2>0.60) on chromosome 2q37. In addition, multiple chromosomal regions showed p-values < 0.0001 for both PP50 and SBP50 training responses. In multivariate models after removing redundant markers, 13 of the most significant SNPs (p<2×10-4 in the GWAS analysis) explained 35.6% of the variance in PP50 training response, while 11 SNPs explained 35.5% of the variance in SBP50 response. The locus on 2q37 accounted for 8.4% and 7.3% of the variance in PP50 and SBP50 responses, respectively. CONCLUSIONS: Our results indicate that multiple SNPs affect genetic variation in hemodynamic training responses, with a locus on chromosome 2q37 having the strongest individual contribution.