Fine mapping of a QTL on chromosome 13 for submaximal exercise capacity training response: The HERITAGE Family Study

Treva K. Rice, Mark A. Sarzynski, Yun Ju Sung, George Argyropoulos, Adrian M. Stütz, Margarita Teran-Garcia, D. C. Rao, Claude Bouchard, Tuomo Rankinen

Research output: Contribution to journalArticlepeer-review

Abstract

Although regular exercise improves submaximal aerobic capacity, there is large variability in its response to exercise training. While this variation is thought to be partly due to genetic differences, relatively little is known about the causal genes. Submaximal aerobic capacity traits in the current report include the responses of oxygen consumption (ΔVO260), power output (ΔWORK60), and cardiac output (ΔQ60) at 60% of VO 2max to a standardized 20-week endurance exercise training program. Genome-wide linkage analysis in 475 HERITAGE Family Study Caucasians identified a locus on chromosome 13q for ΔVO260 (LOD = 3.11). Follow-up fine mapping involved a dense marker panel of over 1,800 single-nucleotide polymorphisms (SNPs) in a 7.9-Mb region (21.1-29.1 Mb from p-terminus). Single-SNP analyses found 14 SNPs moderately associated with both ΔVO 260 at P ≤ 0.005 and the correlated traits of ΔWORK60 and ΔQ60 at P < 0.05. Haplotype analyses provided several strong signals (P < 1.0 × 10~5) for AVO260. Overall, association analyses narrowed the target region and included potential biological candidate genes (MIPEP and SGCG). Consistent with maximal heritability estimates of 23%, up to 20% of the phenotypic variance in ΔVO260 was accounted for by these SNPs. These results implicate candidate genes on chromosome 13q12 for the ability to improve submaximal exercise capacity in response to regular exercise. Submaximal exercise at 60% of maximal capacity is an exercise intensity that falls well within the range recommended in the Physical Activity Guidelines for Americans and thus has potential public health relevance.

Original languageEnglish (US)
Pages (from-to)2969-2978
Number of pages10
JournalEuropean Journal of Applied Physiology
Volume112
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Fitness
  • Genetics
  • MIPEP
  • SGCG
  • SNP

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Public Health, Environmental and Occupational Health
  • Physiology (medical)

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