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

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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 VO2max 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 ΔVO260 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 ΔVO260. 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.

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Acknowledgments

The HERITAGE Family Study is currently supported by NIH/NHLBI grant R01 HL045670. C. Bouchard is partially supported by the John W. Barton Sr. Chair in Genetics and Nutrition. T. Rice and D.C. Rao are also partly supported by NIH/NIGMS grant R01 GM28719. We wish to thank all PIs who contributed to the HERITAGE Family Study in the past via support from the National Heart, Lung, and Blood Institute through the following grants: C Bouchard (HL-45670); AS Leon (HL-47323); DC Rao (HL-47317); JS Skinner (HL-47327); JH Wilmore (HL-47321). The present address for author George Argyropoulos is Weis Center for Research, Geisinger Clinic, Danville, PA 17822-2615, for author Adrian M. Stütz is European Molecular Biology Laboratory, 69117 Heidelberg, Germany, and for author Margarita Teran-Garcia is Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801.

Conflict of interest

The authors declare there are no conflicts of interest.

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Authors and Affiliations

  1. Division of Biostatistics, Washington University, St. Louis, MO, 63110, USA

    Treva K. Rice, Yun Ju Sung & D. C. Rao

  2. Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA, 70808-4124, USA

    Mark A. Sarzynski, George Argyropoulos, Adrian M. Stütz, Margarita Teran-Garcia, Claude Bouchard & Tuomo Rankinen

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  1. Treva K. Rice
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  2. Mark A. Sarzynski
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  3. Yun Ju Sung
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  4. George Argyropoulos
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  6. Margarita Teran-Garcia
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  7. D. C. Rao
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  8. Claude Bouchard
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  9. Tuomo Rankinen
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Correspondence to Tuomo Rankinen.

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Communicated by Martin Flueck.

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Rice, T.K., Sarzynski, M.A., Sung, Y.J. et al. Fine mapping of a QTL on chromosome 13 for submaximal exercise capacity training response: the HERITAGE Family Study. Eur J Appl Physiol 112, 2969–2978 (2012). https://doi.org/10.1007/s00421-011-2274-8

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  • DOI: https://doi.org/10.1007/s00421-011-2274-8

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