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Epigenetics in Sports

Abstract

The heritability of specific phenotypical traits relevant for physical performance has been extensively investigated and discussed by experts from various research fields. By deciphering the complete human DNA sequence, the human genome project has provided impressive insights into the genomic landscape. The hope that this information would reveal the origin of phenotypical traits relevant for physical performance or disease risks has proven overly optimistic, and it is still premature to refer to a ‘post-genomic’ era of biological science. Linking genomic regions with functions, phenotypical traits and variation in disease risk is now a major experimental bottleneck. The recent deluge of genome-wide association studies (GWAS) generates extensive lists of sequence variants and genes potentially linked to phenotypical traits, but functional insight is at best sparse. The focus of this review is on the complex mechanisms that modulate gene expression. A large fraction of these mechanisms is integrated into the field of epigenetics, mainly DNA methylation and histone modifications, which lead to persistent effects on the availability of DNA for transcription. With the exceptions of genomic imprinting and very rare cases of epigenetic inheritance, epigenetic modifications are not inherited transgenerationally. Along with their susceptibility to external influences, epigenetic patterns are highly specific to the individual and may represent pivotal control centers predisposing towards higher or lower physical performance capacities. In that context, we specifically review how epigenetics combined with classical genetics could broaden our knowledge of genotype-phenotype interactions. We discuss some of the shortcomings of GWAS and explain how epigenetic influences can mask the outcome of quantitative genetic studies. We consider epigenetic influences, such as genomic imprinting and epigenetic inheritance, as well as the life-long variability of epigenetic modification patterns and their potential impact on phenotype with special emphasis on traits related to physical performance. We suggest that epigenetic effects may also play a considerable role in the determination of athletic potential and these effects will need to be studied using more sophisticated quantitative genetic models. In the future, epigenetic status and its potential influence on athletic performance will have to be considered, explored and validated using well controlled model systems before we can begin to extrapolate new findings to complex and heterogeneous human populations. A combination of the fields of genomics, epigenomics and transcriptomics along with improved bioinformatics tools and precise phenotyping, as well as a precise classification of the test populations is required for future research to better understand the inter-relations of exercise physiology, performance traits and also susceptibility towards diseases. Only this combined input can provide the overall outlook necessary to decode the molecular foundation of physical performance.

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References

  1. 1.

    Bouchard C, Malina RM. Genetics of physiological fitness and motor performance. Exerc Sport Sci Rev. 1983;11:306–39.

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Rupert J. The search for genotypes that underlie human performance phenotypes. Comparative biochemistry and physiology—part A. Mol Integr Physiol. 2003;136(1):191–203.

    Article  CAS  Google Scholar 

  3. 3.

    Sharp NC. The human genome and sport, including epigenetics and athleticogenomics: a brief look at a rapidly changing field. J Sports Sci. 2008;26(11):1127–33.

    PubMed  Article  Google Scholar 

  4. 4.

    Bouchard C, Lesage R, Lortie G, et al. Aerobic performance in brothers, dizygotic and monozygotic twins. Med Sci Sports Exerc. 1986;18(6):639–46.

    CAS  PubMed  Google Scholar 

  5. 5.

    Maes HH, Beunen GP, Vlietinck RF, et al. Inheritance of physical fitness in 10-yr-old twins and their parents. Med Sci Sports Exerc. 1996;28(12):1479–91.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Peeters MW, Thomis MA, Beunen GP, et al. Genetics and sports: an overview of the pre-molecular biology era. Med Sport Sci. 2009;54:28–42.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Bouchard C, Leon AS, Rao DC, et al. The HERITAGE family study: aims, design, and measurement protocol. Med Sci Sports Exerc. 1995;27(5):721–9.

    CAS  PubMed  Google Scholar 

  8. 8.

    Wilmore JH, Leon AS, Rao DC, et al. Genetics, response to exercise, and risk factors: the HERITAGE Family Study. World Rev Nutr Diet. 1997;81:72–83.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    An P, Perusse L, Rankinen T, et al. Familial aggregation of exercise heart rate and blood pressure in response to 20 weeks of endurance training: the HERITAGE family study. Int J Sports Med. 2003;24(1):57–62.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Bouchard C, An P, Rice T, et al. Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol. 1999;87(3):1003–8.

    CAS  PubMed  Google Scholar 

  11. 11.

    Schmitt-Ney M, Happ B, Ball RK, et al. Developmental and environmental regulation of a mammary gland-specific nuclear factor essential for transcription of the gene encoding beta-casein. Proc Natl Acad Sci USA. 1992;89(7):3130–4.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Dolinoy DC, Weidman JR, Jirtle RL. Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol. 2007;23(3):297–307.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Sato F, Tsuchiya S, Meltzer SJ, et al. MicroRNAs and epigenetics. FEBS J. 2011;278(10):1598–609.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    McNamee MJ, Muller A, van Hilvoorde I, et al. Genetic testing and sports medicine ethics. Sports Med. 2009;39(5):339–44.

    PubMed  Article  Google Scholar 

  15. 15.

    Lippi G, Solero GP, Guidi G. Athletes genotyping: ethical and legal issues. Int J Sports Med. 2004;25(2):159. author reply 60-1.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Bouchard C. Genetics of human obesity: recent results from linkage studies. J Nutr. 1997;127(9):1887S–90S.

    CAS  PubMed  Google Scholar 

  17. 17.

    Perusse L, Gagnon J, Province MA, Rao DC, Wilmore JH, Leon AS, et al. Familial aggregation of submaximal aerobic performance in the HERITAGE Family study. Med Sci Sports Exerc. 2001;33(4):597–604.

    CAS  PubMed  Google Scholar 

  18. 18.

    Peeters MW, Thomis MA, Maes HH, et al. Genetic and environmental determination of tracking in static strength during adolescence. J Appl Physiol. 2005;99(4):1317–26.

    PubMed  Article  Google Scholar 

  19. 19.

    Relton CL. Davey Smith G. Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol. 2012;41(1):161–76.

    PubMed  Article  Google Scholar 

  20. 20.

    Falconer DS. Introduction to quantitative genetics. 2nd ed. London: Longman; 1981.

    Google Scholar 

  21. 21.

    Davids K, Baker J. Genes, environment and sport performance: why the nature-nurture dualism is no longer relevant. Sports Med. 2007;37(11):961–80.

    PubMed  Article  Google Scholar 

  22. 22.

    Montgomery HE, Marshall R, Hemingway H, et al. Human gene for physical performance. Nature. 1998;393(6682):221–2.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Myerson S, Hemingway H, Budget R, et al. Human angiotensin I-converting enzyme gene and endurance performance. J Appl Physiol. 1999;87(4):1313–6.

    CAS  PubMed  Google Scholar 

  24. 24.

    Rankinen T, Wolfarth B, Simoneau JA, et al. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status. J Appl Physiol. 2000;88(5):1571–5.

    CAS  PubMed  Google Scholar 

  25. 25.

    Yang N, MacArthur DG, Gulbin JP, et al. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet. 2003;73(3):627–31.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Norman B, Esbjornsson M, Rundqvist H, et al. Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol. 2009;106(3):959–65.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Saunders CJ, September AV, Xenophontos SL, et al. No association of the ACTN3 gene R577X polymorphism with endurance performance in Ironman Triathlons. Ann Hum Genet. 2007;71(Pt 6):777–81.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Doring FE, Onur S, Geisen U, et al. ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study. J Sports Sci. 2010;28(12):1355–9.

    PubMed  Article  Google Scholar 

  29. 29.

    Hanson ED, Ludlow AT, Sheaff AK, et al. ACTN3 genotype does not influence muscle power. Int J Sports Med. 2010;31(11):834–8.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Puthucheary Z, Skipworth JR, Rawal J, et al. Genetic influences in sport and physical performance. Sports Med. 2011;41(10):845–59.

    PubMed  Article  Google Scholar 

  31. 31.

    Bouchard C. Genetic and molecular aspects of sports performance. Encyclopaedia of sports medicine 18. Chichester: Wiley; 2011.

    Book  Google Scholar 

  32. 32.

    Ruiz JR, Gomez-Gallego F, Santiago C, et al. Is there an optimum endurance polygenic profile? J Physiol. 2009;587(Pt 7):1527–34.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Buxens A, Ruiz JR, Arteta D, et al. Can we predict top-level sports performance in power vs endurance events? A genetic approach. Scand J Med Sci Sports. 2011;21(4):570–9.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Rankinen T, Perusse L, Rauramaa R, et al. The human gene map for performance and health-related fitness phenotypes. Med Sci Sports Exerc. 2001;33(6):855–67.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Roth SM, Rankinen T, Hagberg JM, et al. Advances in exercise, fitness, and performance genomics in 2011. Med Sci Sports Exerc. (epub 9 Feb 2012).

  36. 36.

    Williams AG, Folland JP. Similarity of polygenic profiles limits the potential for elite human physical performance. J Physiol. 2008;586(1):113–21.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Leahy JL. Pathogenesis of type 2 diabetes mellitus. Arch Med Res. 2005;36(3):197–209.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Schroder H. Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes. J Nutr Biochem. 2007;18(3):149–60.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Pratley RE. Gene-environment interactions in the pathogenesis of type 2 diabetes mellitus: lessons learned from the Pima Indians. Proc Nutr Soc. 1998;57(2):175–81.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Huang J, Ellinghaus D, Franke A, et al. 1000 Genomes-based imputation identifies novel and refined associations for the Wellcome Trust Case Control Consortium phase 1 Data. Eur J Hum Genet. (epub 1 Feb 2012).

  41. 41.

    Palmer ND, McDonough CW, Hicks PJ, et al. A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One. 2012;7(1):e29202.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Cho YS, Chen CH, Hu C, et al. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nat Genet. 2012;44(1):67–72.

    CAS  Article  Google Scholar 

  43. 43.

    Kho AN, Hayes MG, Rasmussen-Torvik L, et al. Use of diverse electronic medical record systems to identify genetic risk for type 2 diabetes within a genome-wide association study. J Am Med Inform Assoc. 2012;19(2):212–8.

    PubMed  Article  Google Scholar 

  44. 44.

    Kooner JS, Saleheen D, Sim X, et al. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet. 2011;43(10):984–9.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Cui B, Zhu X, Xu M, et al. A genome-wide association study confirms previously reported loci for type 2 diabetes in Han Chinese. PLoS One. 2011;6(7):e22353.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Below JE, Gamazon ER, Morrison JV, et al. Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals. Diabetologia. 2011;54(8):2047–55.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Parra EJ, Below JE, Krithika S, et al. Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas. Diabetologia. 2011;54(8):2038–46.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Sim X, Ong RT, Suo C, et al. Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet. 2011;7(4):e1001363.

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Florez JC. Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008. J Clin Endocrinol Metab. 2008;93(12):4633–42.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Sottas PE, Robinson N, Fischetto G, et al. Prevalence of blood doping in samples collected from elite track and field athletes. Clin Chem. 2011;57(5):762–9.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Striegel H, Ulrich R, Simon P. Randomized response estimates for doping and illicit drug use in elite athletes. Drug Alcohol Depend. 2010;106(2–3):230–2.

    PubMed  Article  Google Scholar 

  52. 52.

    Simon P, Striegel H, Aust F, et al. Doping in fitness sports: estimated number of unreported cases and individual probability of doping. Addiction. 2006;101(11):1640–4.

    PubMed  Article  Google Scholar 

  53. 53.

    Keller P, Vollaard N, Babraj J, et al. Using systems biology to define the essential biological networks responsible for adaptation to endurance exercise training. Biochem Soc Trans. 2007;35(Pt 5):1306–9.

    CAS  PubMed  Google Scholar 

  54. 54.

    Brantl S. Antisense-RNA regulation and RNA interference. Biochim Biophys Acta. 2002;1575(1–3):15–25.

    CAS  PubMed  Google Scholar 

  55. 55.

    Beiter T, Reich E, Williams RW, et al. Antisense transcription: a critical look in both directions. Cell Mol Life Sci. 2009;66(1):94–112.

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Caplen NJ, Mousses S. Short interfering RNA (siRNA)-mediated RNA interference (RNAi) in human cells. Ann NY Acad Sci. 2003;1002:56–62.

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Rinn JL, Kertesz M, Wang JK, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129(7):1311–23.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Guttman M, Donaghey J, Carey BW, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477(7364):295–300.

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009;23(13):1494–504.

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Moser D, Ekawardhani S, Kumsta R, et al. Functional analysis of a potassium-chloride co-transporter 3 (SLC12A6) promoter polymorphism leading to an additional DNA methylation site. Neuropsychopharmacology. 2009;34(2):458–67.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Gertz J, Varley KE, Reddy TE, et al. Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation. PLoS Genet. 2011;7(8):e1002228.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Nielsen S, Scheele C, Yfanti C, et al. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J Physiol. 2010;588(Pt 20):4029–37.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Davidsen PK, Gallagher IJ, Hartman JW, et al. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. J Appl Physiol. 2011;110(2):309–17.

    PubMed  Article  Google Scholar 

  66. 66.

    Holliday R. Epigenetics: a historical overview. Epigenetics. 2006;1(2):76–80.

    PubMed  Article  Google Scholar 

  67. 67.

    Wu R, Lin M. Functional mapping: how to map and study the genetic architecture of dynamic complex traits. Nat Rev Genet. 2006;7(3):229–37.

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Rakyan VK, Hildmann T, Novik KL, et al. DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project. PLoS Biol. 2004;2(12):e405.

    PubMed  Article  CAS  Google Scholar 

  69. 69.

    Eckhardt F, Lewin J, Cortese R, et al. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet. 2006;38(12):1378–85.

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Park PJ. Epigenetics meets next-generation sequencing. Epigenetics. 2008;3(6):318–21.

    PubMed  Article  Google Scholar 

  71. 71.

    Zilberman D, Henikoff S. Genome-wide analysis of DNA methylation patterns. Development. 2007;134(22):3959–65.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Johannes F, Wardenaar R, Colome-Tatche M, et al. Comparing genome-wide chromatin profiles using ChIP-chip or ChIP-seq. Bioinformatics. 2010;26(8):1000–6.

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Down TA, Rakyan VK, Turner DJ, et al. A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nat Biotechnol. 2008;26(7):779–85.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Rakyan VK, Down TA, Thorne NP, et al. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res. 2008;18(9):1518–29.

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Meissner A, Gnirke A, Bell GW, et al. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res. 2005;33(18):5868–77.

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Schones DE, Zhao K. Genome-wide approaches to studying chromatin modifications. Nat Rev Genet. 2008;9(3):179–91.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Fuks F. DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev. 2005;15(5):490–5.

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Rakyan VK, Blewitt ME, Druker R, et al. Metastable epialleles in mammals. Trends Genet. 2002;18(7):348–51.

    CAS  PubMed  Article  Google Scholar 

  79. 79.

    Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Ann Rev Biochem. 2005;74:481–514.

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Ziller MJ, Muller F, Liao J, et al. Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLoS Genet. 2011;7(12):e1002389.

    CAS  PubMed  Article  Google Scholar 

  81. 81.

    Rottach A, Leonhardt H, Spada F. DNA methylation-mediated epigenetic control. J Cell Biochem. 2009;108(1):43–51.

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008;9(6):465–76.

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Meissner A, Mikkelsen TS, Gu H, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008;454(7205):766–70.

    CAS  PubMed  Google Scholar 

  84. 84.

    Maunakea AK, Nagarajan RP, Bilenky M, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466(7303):253–7.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Weber M, Hellmann I, Stadler MB, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39(4):457–66.

    CAS  PubMed  Article  Google Scholar 

  86. 86.

    Ooi SK, Bestor TH. The colorful history of active DNA demethylation. Cell. 2008;133(7):1145–8.

    CAS  PubMed  Article  Google Scholar 

  87. 87.

    Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol. 2010;11(9):607–20.

    CAS  PubMed  Article  Google Scholar 

  88. 88.

    He YF, Li BZ, Li Z, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303–7.

    CAS  PubMed  Article  Google Scholar 

  89. 89.

    Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–3.

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Zhou VW, Goren A, Bernstein BE. Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet. 2011;12(1):7–18.

    PubMed  Article  CAS  Google Scholar 

  91. 91.

    Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007;448(7153):553–60.

    CAS  PubMed  Article  Google Scholar 

  92. 92.

    Ooi SK, Qiu C, Bernstein E, et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature. 2007;448(7154):714–7.

    CAS  PubMed  Article  Google Scholar 

  93. 93.

    Thomson JP, Skene PJ, Selfridge J, et al. CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature. 2010;464(7291):1082–6.

    CAS  PubMed  Article  Google Scholar 

  94. 94.

    Blackledge NP, Zhou JC, Tolstorukov MY, et al. CpG islands recruit a histone H3 lysine 36 demethylase. Mol Cell. 2010;38(2):179–90.

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Ernst J, Kellis M. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol. 2010;28(8):817–25.

    CAS  PubMed  Article  Google Scholar 

  96. 96.

    Heintzman ND, Hon GC, Hawkins RD, et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature. 2009;459(7243):108–12.

    CAS  PubMed  Article  Google Scholar 

  97. 97.

    Tilgner H, Nikolaou C, Althammer S, et al. Nucleosome positioning as a determinant of exon recognition. Nat Struct Mol Biol. 2009;16(9):996–1001.

    CAS  PubMed  Article  Google Scholar 

  98. 98.

    Luco RF, Pan Q, Tominaga K, et al. Regulation of alternative splicing by histone modifications. Science. 2010;327(5968):996–1000.

    CAS  PubMed  Article  Google Scholar 

  99. 99.

    Rakyan VK, Down TA, Maslau S, et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res. 2010;20(4):434–9.

    CAS  PubMed  Article  Google Scholar 

  100. 100.

    Silva AJ, White R. Inheritance of allelic blueprints for methylation patterns. Cell. 1988;54(2):145–52.

    CAS  PubMed  Article  Google Scholar 

  101. 101.

    Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21.

    CAS  PubMed  Article  Google Scholar 

  102. 102.

    Morgan HD, Santos F, Green K, et al. Epigenetic reprogramming in mammals. Hum Mol Genet. 2005;14 (Spec No 1):R47–58.

    Google Scholar 

  103. 103.

    Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293(5532):1089–93.

    CAS  PubMed  Article  Google Scholar 

  104. 104.

    Farthing CR, Ficz G, Ng RK, et al. Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet. 2008;4(6):e1000116.

    PubMed  Article  CAS  Google Scholar 

  105. 105.

    Zwijnenburg PJ, Meijers-Heijboer H, Boomsma DI. Identical but not the same: the value of discordant monozygotic twins in genetic research. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(6):1134–49.

    CAS  PubMed  Google Scholar 

  106. 106.

    Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102(30):10604–9.

    CAS  PubMed  Article  Google Scholar 

  107. 107.

    Kangaspeska S, Stride B, Metivier R, et al. Transient cyclical methylation of promoter DNA. Nature. 2008;452(7183):112–5.

    CAS  PubMed  Article  Google Scholar 

  108. 108.

    Relton CL, Davey Smith G. Is epidemiology ready for epigenetics? Int J Epidemiol. 2012;41(1):5–9.

    PubMed  Article  Google Scholar 

  109. 109.

    Holliday R. The inheritance of epigenetic defects. Science. 1987;238(4824):163–70.

    CAS  PubMed  Article  Google Scholar 

  110. 110.

    Petronis A. Human morbid genetics revisited: relevance of epigenetics. Trends Genet. 2001;17(3):142–6.

    CAS  PubMed  Article  Google Scholar 

  111. 111.

    Petronis A. Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature. 2010;465(7299):721–7.

    CAS  PubMed  Article  Google Scholar 

  112. 112.

    Makar KW, Perez-Melgosa M, Shnyreva M, et al. Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells. Nat Immunol. 2003;4(12):1183–90.

    CAS  PubMed  Article  Google Scholar 

  113. 113.

    Bennett ST, Wilson AJ, Esposito L, et al. Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group. Nat Genet. 1997;17(3):350–2.

    CAS  PubMed  Article  Google Scholar 

  114. 114.

    Thamotharan M, Garg M, Oak S, et al. Transgenerational inheritance of the insulin-resistant phenotype in embryo-transferred intrauterine growth-restricted adult female rat offspring. Am J Physiol Endocrinol Metab. 2007;292(5):E1270–9.

    CAS  PubMed  Article  Google Scholar 

  115. 115.

    Gluckman PD, Hanson MA, Buklijas T, et al. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol. 2009;5(7):401–8.

    CAS  PubMed  Article  Google Scholar 

  116. 116.

    Hollingsworth JW, Maruoka S, Boon K, et al. In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest. 2008;118(10):3462–9.

    CAS  PubMed  Google Scholar 

  117. 117.

    Oh G, Petronis A. Environmental studies of schizophrenia through the prism of epigenetics. Schizophr Bull. 2008;34(6):1122–9.

    PubMed  Article  Google Scholar 

  118. 118.

    Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–54.

    CAS  PubMed  Article  Google Scholar 

  119. 119.

    Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847–54.

    CAS  PubMed  Article  Google Scholar 

  120. 120.

    Weaver IC. Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let’s call the whole thing off. Epigenetics. 2007;2(1):22–8.

    PubMed  Article  Google Scholar 

  121. 121.

    Lillycrop KA, Burdge GC. Epigenetic changes in early life and future risk of obesity. Int J Obes (Lond). (epub 15 Jun 2010).

  122. 122.

    Burdge GC, Slater-Jefferies J, Torrens C, et al. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr. 2007;97(3):435–9.

    CAS  PubMed  Article  Google Scholar 

  123. 123.

    Ozanne SE, Hales CN. Lifespan: catch-up growth and obesity in male mice. Nature. 2004;427(6973):411–2.

    CAS  PubMed  Article  Google Scholar 

  124. 124.

    Levin BE. Epigenetic influences on food intake and physical activity level: review of animal studies. Obesity (Silver Spring). 2008;16(suppl 3):S51–4.

    PubMed  Article  Google Scholar 

  125. 125.

    Shelnutt KP, Kauwell GP, Gregory JF 3rd, et al. Methylenetetrahydrofolate reductase 677C--> T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem. 2004;15(9):554–60.

    CAS  PubMed  Article  Google Scholar 

  126. 126.

    Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008;105(44):17046–9.

    CAS  PubMed  Article  Google Scholar 

  127. 127.

    Rakyan VK, Beck S. Epigenetic variation and inheritance in mammals. Curr Opin Genet Dev. 2006;16(6):573–7.

    CAS  PubMed  Article  Google Scholar 

  128. 128.

    Chong S, Whitelaw E. Epigenetic germline inheritance. Curr Opin Genet Dev. 2004;14(6):692–6.

    CAS  PubMed  Article  Google Scholar 

  129. 129.

    Morgan HD, Sutherland HG, Martin DI, et al. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23(3):314–8.

    CAS  PubMed  Article  Google Scholar 

  130. 130.

    Roemer I, Reik W, Dean W, et al. Epigenetic inheritance in the mouse. Curr Biol. 1997;7(4):277–80.

    CAS  PubMed  Article  Google Scholar 

  131. 131.

    Dolinoy DC, Das R, Weidman JR, et al. Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatr Res. 2007;61(5 Pt 2):30R–7R.

    PubMed  Article  Google Scholar 

  132. 132.

    Rakyan VK, Chong S, Champ ME, et al. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA. 2003;100(5):2538–43.

    CAS  PubMed  Article  Google Scholar 

  133. 133.

    Lane N, Dean W, Erhardt S, et al. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis. 2003;35(2):88–93.

    CAS  PubMed  Article  Google Scholar 

  134. 134.

    Wolff GL, Kodell RL, Moore SR, et al. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. Faseb J. 1998;12(11):949–57.

    CAS  PubMed  Google Scholar 

  135. 135.

    Cooney CA, Dave AA, Wolff GL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J Nutr. 2002;132(8 Suppl):2393S–400S.

    CAS  PubMed  Google Scholar 

  136. 136.

    Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003;23(15):5293–300.

    CAS  PubMed  Article  Google Scholar 

  137. 137.

    Waterland RA, Travisano M, Tahiliani KG. Diet-induced hypermethylation at agouti viable yellow is not inherited transgenerationally through the female. Faseb J. 2007;21(12):3380–5.

    CAS  PubMed  Article  Google Scholar 

  138. 138.

    Kaminen-Ahola N, Ahola A, Maga M, et al. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet. 2010;6(1):e1000811.

    PubMed  Article  CAS  Google Scholar 

  139. 139.

    Suter CM, Martin DI, Ward RL. Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet. 2004;36(5):497–501.

    CAS  PubMed  Article  Google Scholar 

  140. 140.

    Chan TL, Yuen ST, Kong CK, et al. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat Genet. 2006;38(10):1178–83.

    CAS  PubMed  Article  Google Scholar 

  141. 141.

    Chong S, Youngson NA, Whitelaw E. Heritable germline epimutation is not the same as transgenerational epigenetic inheritance. Nat Genet. 2007;39(5):574–5. author reply 5–6.

    CAS  PubMed  Article  Google Scholar 

  142. 142.

    Hitchins MP, Wong JJ, Suthers G, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med. 2007;356(7):697–705.

    CAS  PubMed  Article  Google Scholar 

  143. 143.

    Horsthemke B. Heritable germline epimutations in humans. Nat Genet. 2007;39(5):573–4. author reply 5–6.

    CAS  PubMed  Article  Google Scholar 

  144. 144.

    Suter CM, Martin DI. Inherited epimutation or a haplotypic basis for the propensity to silence? Nat Genet. 2007;39(5):573. author reply 6.

    CAS  PubMed  Article  Google Scholar 

  145. 145.

    Pembrey ME, Bygren LO, Kaati G, et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet. 2006;14(2):159–66.

    PubMed  Article  Google Scholar 

  146. 146.

    Kaati G, Bygren LO, Edvinsson S. Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet. 2002;10(11):682–8.

    CAS  PubMed  Article  Google Scholar 

  147. 147.

    Wood AJ, Oakey RJ. Genomic imprinting in mammals: emerging themes and established theories. PLoS Genet. 2006;2(11):e147.

    PubMed  Article  CAS  Google Scholar 

  148. 148.

    Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet. 2001;2(1):21–32.

    CAS  PubMed  Article  Google Scholar 

  149. 149.

    Oswald J, Engemann S, Lane N, et al. Active demethylation of the paternal genome in the mouse zygote. Curr Biol. 2000;10(8):475–8.

    CAS  PubMed  Article  Google Scholar 

  150. 150.

    Lewis A, Reik W. How imprinting centres work. Cytogenet Genome Res. 2006;113(1–4):81–9.

    CAS  PubMed  Article  Google Scholar 

  151. 151.

    Jirtle RL. Geneimprint imprinted gene databases: by Species 2012 [online]. http://www.geneimprint.com/site/genes-by-species.Homo+sapiens.any. Accessed 30 Jan 2012.

  152. 152.

    Reik W, Walter J. Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote. Nat Genet. 2001;27(3):255–6.

    CAS  PubMed  Article  Google Scholar 

  153. 153.

    Smith FM, Garfield AS, Ward A. Regulation of growth and metabolism by imprinted genes. Cytogenet Genome Res. 2006;113(1–4):279–91.

    CAS  PubMed  Article  Google Scholar 

  154. 154.

    Delaval K, Wagschal A, Feil R. Epigenetic deregulation of imprinting in congenital diseases of aberrant growth. Bioessays. 2006;28(5):453–9.

    CAS  PubMed  Article  Google Scholar 

  155. 155.

    Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007;211(3):261–8.

    CAS  PubMed  Article  Google Scholar 

  156. 156.

    Plagge A, Isles AR, Gordon E, et al. Imprinted Nesp55 influences behavioral reactivity to novel environments. Mol Cell Biol. 2005;25(8):3019–26.

    CAS  PubMed  Article  Google Scholar 

  157. 157.

    Davies W, Isles A, Smith R, et al. Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice. Nat Genet. 2005;37(6):625–9.

    CAS  PubMed  Article  Google Scholar 

  158. 158.

    Potthoff MJ, Wu H, Arnold MA, et al. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest. 2007;117(9):2459–67.

    CAS  PubMed  Article  Google Scholar 

  159. 159.

    Pandorf CE, Haddad F, Wright C, et al. Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading. Am J Physiol Cell Physiol. 2009;297(1):C6–16.

    CAS  PubMed  Article  Google Scholar 

  160. 160.

    McGee SL, Fairlie E, Garnham AP, et al. Exercise-induced histone modifications in human skeletal muscle. J Physiol. 2009;587(Pt 24):5951–8.

    CAS  PubMed  Article  Google Scholar 

  161. 161.

    McKinsey TA, Zhang CL, Lu J, et al. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature. 2000;408(6808):106–11.

    CAS  PubMed  Article  Google Scholar 

  162. 162.

    Guasconi V, Puri PL. Chromatin: the interface between extrinsic cues and the epigenetic regulation of muscle regeneration. Trends Cell Biol. 2009;19(6):286–94.

    CAS  PubMed  Article  Google Scholar 

  163. 163.

    Terruzzi I, Senesi P, Montesano A, et al. Genetic polymorphisms of the enzymes involved in DNA methylation and synthesis in elite athletes. Physiol Genomics. 2011;43(16):965–73.

    CAS  PubMed  Article  Google Scholar 

  164. 164.

    Barres R, Yan J, Egan B, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012;15(3):405–11.

    CAS  PubMed  Article  Google Scholar 

  165. 165.

    Collins A, Hill LE, Chandramohan Y, et al. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus. PLoS One. 2009;4(1):e4330.

    PubMed  Article  CAS  Google Scholar 

  166. 166.

    Chia DJ, Young JJ, Mertens AR. Distinct alterations in chromatin organization of the two IGF-I promoters precede growth hormone-induced activation of IGF-I gene transcription. Mol Endocrinol. 2010;24(4):779–89.

    CAS  PubMed  Article  Google Scholar 

  167. 167.

    Schwarzenbach H. Impact of physical activity and doping on epigenetic gene regulation. Drug Test Anal. 14 Jun 2011.

  168. 168.

    Wild CP. The exposome: from concept to utility. Int J Epidemiol. 2012;41(1):24–32.

    PubMed  Article  Google Scholar 

  169. 169.

    Herman H, Lu M, Anggraini M, et al. Trans allele methylation and paramutation-like effects in mice. Nat Genet. 2003;34(2):199–202.

    CAS  PubMed  Article  Google Scholar 

  170. 170.

    Anway MD, Cupp AS, Uzumcu M, et al. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308(5727):1466–9.

    CAS  PubMed  Article  Google Scholar 

  171. 171.

    Rando OJ, Verstrepen KJ. Timescales of genetic and epigenetic inheritance. Cell. 2007;128(4):655–68.

    CAS  PubMed  Article  Google Scholar 

  172. 172.

    Johannes F, Colot V, Jansen RC. Epigenome dynamics: a quantitative genetics perspective. Nat Rev Genet. 2008;9(11):883–90.

    CAS  PubMed  Article  Google Scholar 

  173. 173.

    Richards EJ. Inherited epigenetic variation: revisiting soft inheritance. Nat Rev Genet. 2006;7(5):395–401.

    CAS  PubMed  Article  Google Scholar 

  174. 174.

    Bossdorf O, Richards CL, Pigliucci M. Epigenetics for ecologists. Ecol Lett. 2008;11(2):106–15.

    PubMed  Google Scholar 

  175. 175.

    Richards EJ. Population epigenetics. Curr Opin Genet Dev. 2008;18(2):221–6.

    CAS  PubMed  Article  Google Scholar 

  176. 176.

    Macarthur DG, North KN. Genes and human elite athletic performance. Hum Genet. 2005;116(5):331–9.

    CAS  PubMed  Article  Google Scholar 

  177. 177.

    Walsh NP, Gleeson M, Shephard RJ, et al. Position statement. Part one: immune function and exercise. Exerc Immunol Rev. 2011;17:6–63.

    PubMed  Google Scholar 

  178. 178.

    Nakajima K, Takeoka M, Mori M, et al. Exercise effects on methylation of ASC gene. Int J Sports Med. 2010;31(9):671–5.

    CAS  PubMed  Article  Google Scholar 

  179. 179.

    Flanagan JM, Popendikyte V, Pozdniakovaite N, et al. Intra- and interindividual epigenetic variation in human germ cells. Am J Hum Genet. 2006;79(1):67–84.

    CAS  PubMed  Article  Google Scholar 

  180. 180.

    Gerrits A, Li Y, Tesson BM, Bystrykh LV, Weersing E, Ausema A, et al. Expression quantitative trait loci are highly sensitive to cellular differentiation state. PLoS Genet. 2009;5(10):e1000692.

    PubMed  Article  CAS  Google Scholar 

  181. 181.

    International_Human_Genome_Sequencing_Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004 Oct 21;431(7011):931–45.

  182. 182.

    Mendel JG. Versuche über Pflanzenhybriden. Verhandlungen des naturforschenden Vereines in Brünn. 1866, Bd. IV:3–47.

  183. 183.

    Beadle GW, Tatum EL. Genetic control of biochemical reactions in neurospora. Proc Natl Acad Sci USA. 1941;27(11):499–506.

    CAS  PubMed  Article  Google Scholar 

  184. 184.

    Gerstein MB, Bruce C, Rozowsky JS, et al. What is a gene, post-ENCODE? History and updated definition. Genome Res. 2007;17(6):669–81.

    CAS  PubMed  Article  Google Scholar 

  185. 185.

    Kapranov P, Cheng J, Dike S, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007;316(5830):1484–8.

    CAS  PubMed  Article  Google Scholar 

  186. 186.

    Morris KV, Santoso S, Turner AM, et al. Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 2008;4(11):e1000258.

    PubMed  Article  CAS  Google Scholar 

  187. 187.

    Nagano T, Mitchell JA, Sanz LA, et al. The air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science. 2008;322(5908):1717–20.

    CAS  PubMed  Article  Google Scholar 

  188. 188.

    Martianov I, Ramadass A. Serra Barros A, et al. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature. 2007;445(7128):666–70.

    CAS  PubMed  Article  Google Scholar 

  189. 189.

    Ohno M, Fukagawa T, Lee JS, et al. Triplex-forming DNAs in the human interphase nucleus visualized in situ by polypurine/polypyrimidine DNA probes and antitriplex antibodies. Chromosoma. 2002;111(3):201–13.

    CAS  PubMed  Article  Google Scholar 

  190. 190.

    Mariner PD, Walters RD, Espinoza CA, et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol Cell. 2008;29(4):499–509.

    CAS  PubMed  Article  Google Scholar 

  191. 191.

    Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. 2008;320(5881):1336–41.

    CAS  PubMed  Article  Google Scholar 

  192. 192.

    He Y, Vogelstein B, Velculescu VE, et al. The antisense transcriptomes of human cells. Science. 2008;322(5909):1855–7.

    CAS  PubMed  Article  Google Scholar 

  193. 193.

    Schuster SC. Next-generation sequencing transforms today’s biology. Nat Methods. 2008;5(1):16–8.

    CAS  PubMed  Article  Google Scholar 

  194. 194.

    Voelkerding KV, Dames SA, Durtschi JD. Next-generation sequencing: from basic research to diagnostics. Clin Chem. 2009;55(4):641–58.

    CAS  PubMed  Article  Google Scholar 

  195. 195.

    Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111.

    CAS  PubMed  Article  Google Scholar 

  196. 196.

    Lucia A, Moran M, Zihong H, et al. Elite athletes: are the genes the champions? Int J Sports Physiol Perform. 2010;5(1):98–102.

    PubMed  Google Scholar 

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Acknowledgements

The authors have no conflicts of interest to declare that are directly relevant to the content of this review. The authors would like to thank Magdalena Jurkiewicz and Robert Williams for critical reading and discussion of the manuscript. In addition, we highly appreciated the reviewers’ expert recommendations, which were very helpful to further optimize the manuscript.

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Correspondence to Perikles Simon or Dirk A. Moser.

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Ehlert, T., Simon, P. & Moser, D.A. Epigenetics in Sports. Sports Med 43, 93–110 (2013). https://doi.org/10.1007/s40279-012-0012-y

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Keywords

  • Physical Performance
  • Histone Modification
  • Epigenetic Modification
  • Noncoding RNAs
  • Elite Athlete