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Precision Sports Medicine: The Future of Advancing Health and Performance in Youth and Beyond

Montalvo, Alicia M. PhD, LAT, ATC, CSCS1; Tse-Dinh, Yuk-Ching PhD2,3; Liu, Yuan MD, PhD2,3; Swartzon, Michael MD, FAAFP4; Hechtman, Keith S. MD4; Myer, Gregory D. PhD, CSCS*D5,6,7,8,9

Author Information
Strength and Conditioning Journal: April 2017 - Volume 39 - Issue 2 - p 48-58
doi: 10.1519/SSC.0000000000000292
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In his State of the Union Address in January 2015, President Obama announced the launch of the Precision Medicine Initiative (PMI) (67). The intention of the PMI is “to bring us closer to curing diseases like cancer and diabetes, and to give all of us access to the personalized information we need to keep ourselves and our families healthier” (67). Precision medicine is an individualized approach to prevention, diagnosis, and treatment of disease (56). This individualized approach focuses on the unique variability in genes, lifestyle, and environment of each person (12). Sequencing of the human genome and the subsequent development of methods and tools for analyzing large sets of data have created opportunities for innovative and personalized approaches to clinical practice (23).

The Human Genome Project, which entailed the mapping and understanding of all human genes, was completed in 2003 (9,11). This discovery laid the groundwork for the proliferation of precision medicine. Completion of genome-wide association studies (GWAS), or studies that analyze complete genomes to find genetic variants associated with a specific disease, made it possible to identify genetic contributions to the development of disease (8).

Although the immediate focus of precision medicine is related to prevention and treatment of cancer, the long-term focus is to advance knowledge of personalized medicine in all areas of health and disease (23). This review is intended to provide an introduction to the fundamental components of precision medicine to practitioners. These components include genetics and genomics, epigenetics and biomarkers, environment and lifestyle, among others. Not only is it possible to tailor some medical interventions based on molecular characteristics, but it is also possible to tailor training regimens in certain individuals to maximize sports performance. Both sports medicine and strength and conditioning practitioners should be aware of advances in precision medicine to capitalize on these concepts that may eventually influence decision-making in the clinic, athletic training room and, ultimately, on the field of play.


Genetics is the study of individual genes and their role in heredity (3). Genes, the basic units of heredity, are composed of DNA base pairs (15). DNA provides the instructions for genes, genes provide the instructions for the production of proteins, and proteins contribute to the functioning of the cells and body as a whole (2). There are approximately 20,000–25,000 genes in the human genome (15). Differences among individuals (hair color, eye color, etc.) result from alleles, or different versions of the same gene (13).

The study of all the genes (genome) and their interaction with one another and the environment is known as genomics (3). Analysis of genes and the genome is accomplished through bioinformatics, a subdiscipline of science that combines biology, computer science, statistics, and mathematics to analyze large sets of genetic data (1). Bioinformatics has enabled the identification of single nucleotide polymorphisms (SNPs). SNPs are common genetic variations that result from a single nucleotide being replaced by another (Figure 1) (14). For example, where most individuals in a population may have a thymine nucleotide, a small subset of individuals may have a cytosine nucleotide in the same location on the genome. The effect of the SNP depends on its location (14). If an SNP is located in a gene coding region or a region that regulates a gene, an individual's susceptibility to disease or injury or response to a stimulus, such as training, may be altered (14).

Figure 1.
Figure 1.:
Depiction of an example of a single nucleotide polymorphism (SNP) and its result on the end product in protein synthesis. A) A normal nucleotide base pair for a given location on the genotype and the resultant protein. B) A SNP at the same location with changes to the resultant protein. Reprinted from Journal of the Academy of Nutrition and Dietetics, 114/2, Kathryn M. Camp, Elaine Trujillo, Position of the Academy of Nutrition and Dietetics: Nutritional Genomics, 299–312, Copyright (2014), with permission from Elsevier.

Diseases at least partially attributed to SNPs include Huntington's disease and different types of cancers (40). Identification of SNPs in genes associated with these diseases (the Huntington gene mutation that results in Huntington's disease and the mutations in BRCA1 and BRCA2 genes that result in breast and ovarian cancers, respectively) has led to early detection of disease through genetic testing (6,7).

Specific to sports medicine, SNPs that contribute to soft tissue injury have been identified (42,64,65,75). Collagen, a protein that comprises ligaments and other soft tissue in the body, is coded for by a variety of collagen genes (85). SNPs within various collagen-encoding genes have been correlated with musculoskeletal injury in humans. Individuals with these genetic variants are at increased risk of anterior cruciate ligament (ACL) rupture, Achilles tendon rupture, and shoulder dislocation (42,64,65,75). Genetic contribution to injury is further supported by a twin study that showed fraternal twins demonstrating similar high-risk landing mechanics and ACL injury patterns (36). Female twins who subsequently experienced ACL injury also demonstrated decreased peak knee flexion at landing, increased joint laxity, decreased quadriceps-to-hamstring torque, and decreased intercondylar notch width relative to uninjured controls (29). A combination twin and familial study led to the identification of SNPs not previously known to be associated with ACL injury, further emphasizing the genetic predisposition to ligamentous injury (21). Furthermore, research indicates that individuals who have sustained ACL injury are more likely to have ACL injured relatives than individuals who have not sustained ACL injury (28,44).

These findings suggest a strong genetic predisposition to injury, which is a passive risk factor for injury (17,18). Currently, passive risk factors for injury are nonmodifiable. By contrast, active risk factors, such as landing with knees extended and/or reliance on frontal plane control strategies during landing, are modifiable to a greater extent than passive risk factors through proper neuromuscular training (17,18,37). To optimize the effects of neuromuscular training, especially for youth with both passive and active risk factors, ACL injury prevention programs should be initiated at younger ages to precede changes associated with growth and maturation. Additional training should be provided to coaches to help mitigate the effects of pubertal growth without matched adaptive response with strength and neuromuscular control (34). In addition, practitioners should consider implementing screening tools to identify these nonmodifiable risk factors to implement strategies that mitigate the risk of injury in genetically predisposed athletes. These strategies could include collecting a detailed family history related to musculoskeletal injury, assessing for joint laxity and strength and neuromuscular asymmetry, and implementing movement screening (50–55).

Regarding performance, precision medicine can be used to personalize training. Several SNPs associated with exercise-induced muscle damage have been identified (20). These SNPs include ACTN3, TNF, and IGF2, but only ACTN3 will be discussed here as an example (20). The ACTN3 SNP entails the substitution of a cytosine nucleotide with a thyamine nucleotide. Individuals with this SNP do not express an arginine amino acid which results in an inability to express the α-actinin-3 protein (20). The deficiency in this protein is associated with decreased muscle volume, strength, and power (i.e., alterations in fast-twitch muscle fibers) and increases in susceptibility to the effects of intense exercise relative to those without a deficiency (22,24,27,49,58,63,76,77,83). In addition to muscle damage, SNPs associated with power performance have also been identified. The TT genotype of CNTFR SNP was significantly more frequent in elite power athletes than in controls (47). Given this information about athletes, practitioners may be able to make better decisions about how to structure the training of athletes without the polymorphism to maximize power. Practitioners with access to information about an athlete's ability to recover from strenuous training and how they respond to training may be able to maximize training prescriptions and reduce the risk of injury (20). Identification of relevant SNPs in these athletes could be used to personalize training regimens. Currently, athletes train together as scheduled, but perhaps a more effective means of improving performance would be to individualize training and recovery by genotype.

Although advances in prevention and treatment of SNP-associated diseases still lag behind our ability to identify them, identification of these SNPs has provided opportunities for the development of novel personalized interventions. For example, several patents have been filed for genetic tests to identify individuals who may be at risk of injury to tendons and ligaments (74). Companies that specialize in genetic testing of athletes analyze the genome for known genetic variants in different categories, including performance capabilities and injury risk (33). There are also companies that offer testing for specific SNPs for a fixed rate. Although genetic testing alone cannot predict tendinous or ligamentous injury, it is another nonmodifiable risk factor to be considered in injury prevention and performance enhancement strategies. Practitioners without access to genetic testing should be aware of genetic contributions to risk of injury and responses to training and recovery. By simply being well informed, practitioners can make efforts to mitigate the risks of genetic contributions to injury and to recognize that athletes will have unique responses to training. Practical applications for integrating genetics and genomics into training are listed in Table 1. Advances in science may eventually lead to new approaches to prevention using genetic intervention.

Table 1
Table 1:
Practical applications for genetics and genomics


Although genes are the basic units of heredity, there is growing evidence that the contribution of genes to disease only accounts for a small proportion of disease risk (missing heritability) (59). The genome is predetermined and concrete; however, disease can result without genetic predisposition. This may be due to the gene-environment interaction (GEI), which can result in higher risk of specific diseases, or due to differences in environmental exposures.

The GEI is the idea that disease results from a combination of an individual's genes and environmental factors (4,61). These environmental factors can be classified as physical, chemical, biological, behavioral, etc., and include exposure to pollution, ingestion of medication, and different types of foods, etc (4,61). Essentially, GEI dictates that genetic differences will cause individuals to respond to the environment in different ways (4). Evidence in support of GEI in medicine indicates that number of births to women with the LSP1 gene variant and alcohol consumption in women with the CASP8 gene variant are associated with an increased risk of developing breast cancer (57). These data indicate that differences in environmental exposure (number of births, alcohol consumption) change the outcome (risk of breast cancer) in women with the same genotype (LSP1, CASP8).

In addition to the GEI, it is likely that environmental exposures result in changes regardless of genotype. In a study of twins (identical and non-identical), where one twin developed Parkinson's Disease and the other did not, exposure to the chemical trichloroethylene, a commonly used engine degreaser and agent to extract oils from plants, was associated with an increased risk of developing the disease (31). This finding showed that individuals who shared identical or similar genomes did not share disease risk in the presence of an environmental exposure.

Regarding sports medicine, there is growing concern about the association between ACL injury and the subsequent development of osteoarthritis. Research indicates that individuals who have undergone unilateral anterior cruciate ligament reconstruction (ACLR) have a 3-fold increase in prevalence of osteoarthritis in the affected knee compared with the unaffected knee (19). This result suggests that the environmental exposure (either injury or ACLR) is, by some mechanism, contributing to an increase in the risk of disease (osteoarthritis). This finding highlights the importance of the role of the strength and conditioning practitioner. First, steps should be taken to prevent both initial ACL injury and initial injury to synovial joints in general to reduce the risk of negative lifetime outcomes. Second, care should be taken in selecting appropriate return-to-play protocols to ensure that athletes are indeed prepared to play to reduce the risk of rerupture. Practitioners have a variety of tools at their disposal, including identification of genetic predisposition to injury, movement screens, and the implementation of preventive exercise programs. Practical applications for environment and lifestyle are listed in Table 2.

Table 2
Table 2:
Practical applications for environment and lifestyle

Specific to sport performance, a commonly studied exposure is nutrition. Individuals will respond to exercise differently based on nutrition status because of changes in gene expression, which are further explored in the next section. Interleukin-6 (IL-6) is an inflammatory cytokine that is an indicator of exercise-induced muscle damage (41). Under low glycogen conditions, IL-6 concentrations were significantly higher than under high glycogen and control conditions (41). Increased concentrations of IL-6 are correlated with decreased sport performance (70,71). These findings emphasize the importance of both proper nutrition and proper recovery from exercise. In the case of decreasing athletic performance, practitioners should be aware of the role nutrition plays. Athletes, especially youth athletes, may not be aware of the influence of nutrition on performance and recovery. As such, practitioners should provide athletes with strategies to improve food choices to enhance training and performance from an exposure perspective.

By developing an understanding of environmental exposures, including behaviors or events that may increase the risk of disease, it may be possible to provide intervention strategies to mitigate or remove exposures (e.g., alcohol consumption education program for women with the CASP8 gene variant to reduce the risk of breast cancer; new safety guidelines for workers exposed to trichloroethylene to reduce the risk of Parkinson's Disease; ACL injury prevention programs). It may also provide opportunities for novel prevention and treatment of pathology. Although some environmental factors that result in disease may be apparent, future research should focus on identifying novel exposures, such as the effect of lifetime exposure to physical activity on injury risk or athletic performance potential. In addition, traditional exposures, such as diet, amount of sleep, and family environment, should be more specifically investigated to identify their effects on gene expression and, subsequently, injury risk and sport performance.


The preceding section on environment and lifestyle leads to the concept of epigenetics. Epigenetics is defined as “the study of changes in gene function that are heritable and that do not entail a change in DNA sequence” (86). As previously mentioned, the genome is inherited and stable. However, there can be changes made during the process of gene expression that result in changes to gene function. The changes in gene expression can result from factors related to environment and lifestyle, such as exposure to pollutants and lack of exercise.

An understanding of gene expression requires an understanding of foundational concepts. The genes, and more specifically the alleles an individual inherits, are known as a genotype. The outward expression of that genotype is known as phenotype. Gene expression depends on ribonucleic acid (RNA) transcription and translation (Figure 2). Transcription occurs when RNA is made from a section of DNA (10). Translation occurs when the RNA that was made through transcription is used to make amino acids during protein synthesis (10). Epigenetic modifications, which include DNA methylation, histone modification, and microRNA (miRNA) expression, result in changes to gene expression. Gene expression is the phenotypic, or outward, manifestation resulting from the sequential processes of transcription and translation and is regulated by epigenetic modifications (5,30). The environmental factors previously discussed can result in epigenetic modifications that cause genes to either be activated (expressed) or deactivated (suppressed).

Figure 2.
Figure 2.:
Illustration of the processes of deoxyribonucleic acid (DNA) transcription and translation. During transcription, DNA is used to make RNA. During translation, RNA is used to make amino acids during protein synthesis. Reprinted from Journal of the Academy of Nutrition and Dietetics, 114/2, Kathryn M. Camp, Elaine Trujillo, Position of the Academy of Nutrition and Dietetics: Nutritional Genomics, 299–312, Copyright (2014), with permission from Elsevier.

In medicine, inflammation resulting from endogenous and environmental stress is a known contributor to the development of some cancers (26). The presence of inflammation caused by infection, smoking, obesity, etc. can lead to DNA methylation (epigenetic modification), and, subsequently, changes to gene expression (35,78). Cellular signaling chemicals, such as cytokines, which include the interleukin family, interferons, transforming growth factor beta family (TNF-β) among others, promote the inflammatory response. They mediate the inflammation-induced epigenetic modifications that alter gene expression and ultimately lead to the development of cancer (89). It has been found that cytokines can induce epigenetic changes in DNA methylation, histone modifications, and miRNA expression (72). These changes then alter the expression of multiple genes by inducing the enzymes that methylate DNA, inducing or suppressing several forms of miRNA, and altering changes to synthesized proteins at specific genes. This results in cell transformation and leads to the initiation and progression of cancer (80). As such, cytokines can be useful for determining initiation, diagnosis, prognosis of, and developing treatments for cancer.

In athletes, exposure to traumatic knee joint injury (e.g., ACL injury, reconstruction) and abnormal loading patterns results in the development of osteoarthritis (32). An SNP on the GDF5 gene has been associated with susceptibility to osteoarthritis in GWAS (48). The gene is part of the TNF-β family and plays a role in maintaining and repairing synovial joints (43). Expression of the thyamine nucleotide instead of the cytosine nucleotide in a specific location of the GDF5 is associated with osteoarthritis susceptibility; therefore, expression of the cytosine nucleotide is preferred in cartilage and joints (25). Upregulation of the GDF5 gene results in expression of the cytosine allele of the SNP (68). Research indicates that GDF5 upregulation is correlated with DNA demethylation, which is an epigenetic modification (68). This finding allows for the development of novel pathways to prevent disease. In this case, interventions (lifestyle or other) can be created to upregulate the GDF5 gene to decrease the susceptibility to developing osteoarthritis. Interventions like these are particularly important to youth athletes who have not experienced the negative sequelae of injury. Early intervention could lead to increased lifetime physical activity and decreased healthcare costs later in life. However, more research is needed to determine the effects of current interventions/exposure conditions on epigenetic modifications. For example, the effects of ACL surgery type (autograft versus allograft), length of rehabilitation, and return-to-play protocols, among many others, on GDF5 expression should be identified to make clinical decisions that reduce the risk of developing osteoarthritis later in life.

Regarding training, epigenetic modifications associated with muscle development have been identified. Suppression of the MEF2 gene in rats through histone modification resulted in a decrease in the formation of slow-twitch muscle fibers (66). For humans, this would result in increased ability to produce power. Furthermore, histone modifications to the MHC genes in rats altered the expression of muscle fiber type (62). Histone modifications dictated whether muscle fiber types would be slow- or fast-twitch (62); although, in rats, these findings suggest that muscle function can be altered to best suit the demands of the sport. However, because epigenetics in human performance is a nascent topic, the ability for practitioners to apply findings is still in the developmental stages. Similar to upregulation of the GDF5 gene, future research should focus on how to alter gene expression to optimize sport performance. In the case of MEF2/MHC genes, future research should identify what environmental and lifestyle factors can be altered to achieve the optimal muscle fiber type profile for a given athlete.



Pharmacogenomics is a subdiscipline of both pharmacology and genomics (16). Pharmacogenomics is the study of how genes affect an individual's response to a drug (16). The influence of genetic factors on pharmacokinetics and pharmacodynamics can be important determinants of both adverse events and clinical outcomes. In patients with atrial fibrillation, 2 genotypes (CYP2C9 and VKORC1) were identified as being associated with early bleeding with the drug warfarin and as responding more safely to the drug exoban (46). Evidence exists to support the notion that outcomes can be improved by taking into account an individual's genetic makeup.

The application of pharmacogenomics in sports medicine extends mainly to individual response to anti-inflammatory drugs. The pharmacokinetics of S-ibuprofen and R-ibuprofen was found to be affected by CYP2C9 polymorphisms and sex (60). Pharmacogenetics and pharmacogenomics are highly relevant for personalized pain management because multiple gene-gene and GEIs can influence pain perception and response to analgesia (87). Heterogeneity of therapeutic response and adverse events to asthma medication are also of significance for sports medicine (73). Future research should employ GWAS to investigate the effect of genetics on response to commonly used drugs, especially in the case of pathologies that are difficult to treat (e.g., knee joint effusion, tendiopathy, etc.).


The human microbiome refers to the different types of microbes found in the human body and their genes (82). The microbiome plays a role in human resistance and susceptibility to disease, especially inflammatory disease (84). Metagenomics is the genetic analysis of all the genomes within an environmental sample (81). For humans, this means analysis of both the genome and the microbiome. Research indicates that disruptions in the intestinal microbiome may contribute to the development of type 1 diabetes, type 2 diabetes, and obesity (79). This knowledge helps to provide novel pathways for the prevention of disease.

The link between the human microbiome and asthma can be relevant to sports medicine (69). The lung microbiomes of healthy and asthmatic individuals were found to differ, and the lower airway microbiota was related to measures of asthma severity (38,90). Asthmatics had significantly greater pathogenic bacteria than nonasthmatics (38). The intestinal microbiome influences the immune response that mediates allergy and asthma (29,45). These findings suggest that the presence of harmful bacteria inherent to some individuals can negatively influence athletic performance. Research is needed to determine if regulation of the lung and intestinal microbiomes could have a positive effect on athletic performance (39).

Microbiomes are of particular concern in skin conditions. Microbial communities found in athletic equipment in gyms are shaped by interactions with human skin (88). Mats and floors in gyms were found to have the greatest concentrations of bacteria, likely transmitted through human skin, human sweat, and foot traffic (88). These findings are of particular relevance to sports on mats (wrestling, gymnastics) and to athletes who play on turf. There are also implications of the interactions among skin, the microbiome, and athletic equipment for preventing and/or treating methicillin-resistant Staphylococcus aureus (MRSA). Future research in sports medicine should identify behaviors that could result in decreased transmission of skin microbiota, new techniques for disinfecting surfaces, and novel interventions for MRSA to decrease the risk of acquiring and spreading skin conditions.


Precision medicine combines components from various emerging sciences to improve desired outcomes. Genetics and genomics are used to identify genes and gene variants that result in disease. This information can be used for early detection of conditions that predispose athletes to injury, deciding whether or not an athlete will respond to a particular type of intervention or training, and determining treatment through pharmacogenomics. Individuals' environments and lifestyles influence the way genes and the genome function. Environmental exposures should be taken into consideration to reduce risk of negative outcomes from injury later in life, and to enhance performance in the present. Epigenetic changes result from an interaction between an individual's genes and their environment and determine the outward expression of those genes. This field is not yet advanced enough in terms of human research to make recommendations for practice.

Because precision medicine concepts are so new to sports medicine and strength and conditioning, it is difficult to make more specific suggestions for strategies to incorporate them into practice. To allow for growth in precision medicine as it relates to these fields, it is important for practitioners and researchers with laboratory scientists to facilitate translational research. Currently, genetics is already being used to identify individuals who may be at risk of injury and those who may respond best to training. There are opportunities within the subdiscipline of pharmacogenetics to identify preventive strategies or therapeutic interventions that may work best for specific genotypes. This may lead to enhanced healing after sport injury and improved sport performance through personalized training prescriptions. Nontraditional factors related to environment and lifestyle should be investigated to determine their contributions to sport injury and performance. Moreover, the effect of these exposures on gene expression and their mechanisms should be studied, and the results used to quantify risk of injury and identify effects on sports performance. This may allow for the creation of novel interventions to reduce injury risk and enhance sports performance.

Advances in precision medicine and cancer research are creating a new framework for interdisciplinary research. Just as oncologists and basic science researchers must work together toward the goal of curing cancer, practitioners and basic science researchers must work together to make creative discoveries in injury prevention and performance enhancement. By following the principles of precision medicine, it is possible for practitioners to find new and personalized ways to prevent injuries and enhance performance. By targeting precision medicine efforts at prevention and training in youth athletes, it is possible to improve long-term outcomes to ensure that this cohort remains healthy and physically active throughout their lifetime.


1. Bioinformatics: Introduction. Available at: Accessed: November 28, 2016.
2. Fact Sheet 1: An Introduction to DNA, Genes and Chromosomes. Available at: Accessed: November 28, 2016.
3. Frequently Asked Questions About Genetic and Genomic Science. Available at: Accessed: November 28, 2016.
4. Gene-Environment Interaction. Available at: Accessed: November 28, 2016.
5. Gene Expression. Available at: Accessed: November 28, 2016.
6. Genes and Disease: Breast and Ovarian Cancer [Internet]. Available at: Accessed: November 28, 2016.
7. Genes and Disease: Huntington Disease [Internet]. Available at: Accessed: November 28, 2016.
8. Genome-Wide Association Studies. Available at: Accessed: November 28, 2016.
9. The Human Genome Project Completion: Frequently Asked Questions. Available at: Accessed: November 28, 2016.
10. Internet-Based Tools for Teaching Transcription and Translation. Available at: Accessed: November 28, 2016.
11. An Overview of the Human Genome Project. Available at: Accessed November 28, 2016.
12. Precision Medicine Initiative Cohort Program. Available at: Accessed: November 28, 2016.
13. Talking Glossary of Genetic Terms: Allele. Available at: Accessed: November 28, 2016.
14. What Are Single Nucleotide Polymorphisms (SNPs)? Available at: Accessed: November 28, 2016.
15. What Is a Gene? Available at: Accessed: November 28, 2016.
16. What Is Pharmacogenomics? Available at: Accessed: November 28, 2016.
17. Alentorn-Geli E, Mendiguchía J, Samuelsson K, Musahl V, Karlsson J, Cugat R, Myer G. Prevention of non-contact anterior cruciate ligament injuries in sports. Part II: Systematic review of the effectiveness of prevention programmes in male athletes. Knee Surg Sports Traumatol Arthrosc 22: 16, 2014.
18. Alentorn-Geli E, Myer GD, Silvers HJ, Samitier G, Romero D, Lázaro-Haro C, Cugat R. Prevention of non-contact anterior cruciate ligament injuries in soccer players. Part 1: Mechanisms of injury and underlying risk factors. Knee Surg Sports Traumatol Arthrosc 17: 705, 2009.
19. Barenius B, Ponzer S, Shalabi A, Bujak R, Norlén L, Eriksson K. Increased risk of osteoarthritis after anterior cruciate ligament reconstruction a 14-year follow-up study of a randomized controlled trial. Am J Sports Med 42: 1049–1057, 2014.
20. Baumert P, Lake MJ, Stewart CE, Drust B, Erskine RM. Genetic variation and exercise-induced muscle damage: Implications for athletic performance, injury and ageing. Eur J Appl Physiol 116: 1595–1625, 2016.
21. Caso E, Maestro A, Sabiers CC, Godino M, Caracuel Z, Pons J, Gonzalez FJ, Bautista R, Claros MG, Caso-Onzain J, Viejo-Allende E, Giannoudis PV, Alvarez S, Maietta P, Guerado E. Whole-exome sequencing analysis in twin sibling males with an anterior cruciate ligament rupture. Injury 47(Suppl 3): S41–S50, 2016.
22. Clarkson PM, Devaney JM, Gordish-Dressman H, Thompson PD, Hubal MJ, Urso M, Price TB, Angelopoulos TJ, Gordon PM, Moyna NM. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol (1985) 99: 154–163, 2005.
23. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med 372: 793–795, 2015.
24. Deuster PA, Contreras-Sesvold CL, O'Connor FG, Campbell WW, Kenney K, Capacchione JF, Landau ME, Muldoon SM, Rushing EJ, Heled Y. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol 113: 1997–2004, 2013.
25. Egli R, Southam L, Wilkins J, Lorenzen I, Pombo-Suarez M, Gonzalez A, Carr A, Chapman K, Loughlin J. Functional analysis of the GDF5 regulatory polymorphism that is associated with OA susceptibility. Arthritis Rheum 60: 2055–2064, 2009.
26. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13: 759–771, 2013.
27. Erskine RM, Williams AG, Jones DA, Stewart CE, Degens H. The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training. Scand J Med Sci Sports 24: 642–648, 2014.
28. Flynn RK, Pedersen CL, Birmingham TB, Kirkley A, Jackowski D, Fowler PJ. The familial predisposition toward tearing the anterior cruciate ligament a case control study. Am J Sports Med 33: 23–28, 2005.
29. Fujimura KE, Lynch SV. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe 17: 592–602, 2015.
30. Gibney E, Nolan C. Epigenetics and gene expression. Heredity (Edinb) 105: 4–13, 2010.
31. Goldman SM, Quinlan PJ, Ross GW, Marras C, Meng C, Bhudhikanok GS, Comyns K, Korell M, Chade AR, Kasten M. Solvent exposures and Parkinson disease risk in twins. Ann Neurol 71: 776–784, 2012.
32. Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol 23: 471, 2011.
33. Goodlin GT, Roos TR, Roos AK, Kim SK. The dawning age of genetic testing for sports injuries. Clin J Sports Med 25: 1, 2015.
34. Grandhi RK, Sugimoto D, Posthumus M, Schneider D, Myer GD. The dynamic interplay between active and passive knee stability: Implications for management of the high ACL injury risk athlete. In: Rotatory Knee Instability. New York, NY: Springer, 2017, pp: 473–490.
35. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 140: 883–899, 2010.
36. Hewett TE, Lynch TR, Myer G, Ford K, Gwin R, Heidt R. Multiple risk factors related to familial predisposition to anterior cruciate ligament injury: Fraternal twin sisters with anterior cruciate ligament ruptures. Br J Sports Med 44: 848–855, 2010.
37. Hewett TE, Myer GD. The mechanistic connection between the trunk, knee, and anterior cruciate ligament injury. Exerc Sport Sci Rev 39: 161, 2011.
38. Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, Davies J, Ervine A, Poulter L, Pachter L. Disordered microbial communities in asthmatic airways. PLoS One 5: e8578, 2010.
39. Hsu YJ, Chiu CC, Li YP, Huang WC, Te Huang Y, Huang CC, Chuang HL. Effect of intestinal microbiota on exercise performance in mice. J Strength Cond Res 29: 552–558, 2015.
40. Johnson N, Fletcher O, Palles C, Rudd M, Webb E, Sellick G, dos Santos Silva I, McCormack V, Gibson L, Fraser A. Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility. Hum Mol Genet 16: 1051–1057, 2007.
41. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, Neufer PD. Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: Influence of muscle glycogen content. FASEB J 15: 2748–2750, 2001.
42. Khoschnau S, Melhus H, Jacobson A, Rahme H, Bengtsson H, Ribom E, Grundberg E, Mallmin H, Michaëlsson K. Type I collagen α 1 Sp1 polymorphism and the risk of cruciate ligament ruptures or shoulder dislocations. Am J Sports Med 36: 2432–2436, 2008.
43. Luyten FP. Cartilage-derived morphogenetic protein-1. Int J Biochem Cell Biol 29: 1241–1244, 1997.
44. Martin R, Hugentobler J, Myer G. Is ACL injury all too “familial” for some patients? Sports Physio 2: 19–24, 2011.
45. McLoughlin RM, Mills KH. Influence of gastrointestinal commensal bacteria on the immune responses that mediate allergy and asthma. J Allergy Clin Immunol 127: 1097–1107, 2011.
46. Mega JL, Walker JR, Ruff CT, Vandell AG, Nordio F, Deenadayalu N, Murphy SA, Lee J, Mercuri MF, Giugliano RP. Genetics and the clinical response to warfarin and edoxaban: Findings from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet 385: 2280–2287, 2015.
47. Miyamoto-Mikami E, Fujita Y, Murakami H, Ito M, Miyachi M, Kawahara T, Fuku N. CNTFR genotype and sprint/power performance: Case-control association and functional studies. Int J Sports Med 37: 411–417, 2016.
48. Miyamoto Y, Mabuchi A, Shi D, Kubo T, Takatori Y, Saito S, Fujioka M, Sudo A, Uchida A, Yamamoto S. A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet 39: 529–533, 2007.
49. Moran CN, Yang N, Bailey ME, Tsiokanos A, Jamurtas A, MacArthur DG, North K, Pitsiladis YP, Wilson RH. Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks. Eur J Hum Genet 15: 88–93, 2007.
50. Myer GD, Ford KR, Brent JL, Hewett TE. An integrated approach to change the outcome part I: Neuromuscular screening methods to identify high ACL injury risk athletes. J Strength Cond Res 26: 2265, 2012.
51. Myer GD, Ford KR, Brent JL, Hewett TE. An integrated approach to change the outcome part II: Targeted neuromuscular training techniques to reduce identified ACL injury risk factors. J Strength Cond Res 26: 2272, 2012.
52. Myer GD, Ford KR, Hewett TE. New method to identify athletes at high risk of ACL injury using clinic-based measurements and freeware computer analysis. Br J Sports Med 45: 238–244, 2011.
53. Myer GD, Ford KR, Khoury J, Hewett TE. Three-dimensional motion analysis validation of a clinic-based nomogram designed to identify high ACL injury risk in female athletes. Phys Sportsmed 39: 19–28, 2011.
54. Myer GD, Ford KR, Paterno MV, Nick TG, Hewett TE. The effects of generalized joint laxity on risk of anterior cruciate ligament injury in young female athletes. Am J Sports Med 36: 1073–1080, 2008.
55. Myer GD, Stroube BW, DiCesare CA, Brent JL, Ford KR, Heidt RS, Hewett TE. Augmented feedback supports skill transfer and reduces high-risk injury landing mechanics a double-blind, randomized controlled laboratory study. Am J Sports Med 41: 669–677, 2013.
56. National Research Council Committee on a Framework for Developing a New Taxonomy of Disease. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington, DC: National Academies Press (US), 2011.
57. Nickels S, Truong T, Hein R, Stevens K, Buck K, Behrens S, Eilber U, Schmidt M, Häberle L, Vrieling A. Evidence of gene–environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genet 9: e1003284, 2013.
58. Niemi AK, Majamaa K. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet 13: 965–969, 2005.
59. Ober C, Vercelli D. Gene–environment interactions in human disease: Nuisance or opportunity? Trends Genet 27: 107–115, 2011.
60. Ochoa D, Prieto-Pérez R, Román M, Talegón M, Rivas A, Galicia I, Abad-Santos F, Cabaleiro T. Effect of gender and CYP2C9 and CYP2C8 polymorphisms on the pharmacokinetics of ibuprofen enantiomers. Pharmacogenomics 16: 939–948, 2015.
61. Ottman R. Gene–environment interaction: Definitions and study designs. Prev Med 25: 764, 1996.
62. Pandorf CE, Haddad F, Wright C, Bodell PW, Baldwin KM. 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 297: C6–C16, 2009.
63. Pimenta EM, Coelho DB, Cruz IR, Morandi RF, Veneroso CE, de Azambuja Pussieldi G, Carvalho MRS, Silami-Garcia E, Fernández JADP. The ACTN3 genotype in soccer players in response to acute eccentric training. Eur J Appl Physiol 112: 1495–1503, 2012.
64. Posthumus M, September AV, Keegan M, O'Cuinneagain D, Van der Merwe W, Schwellnus MP, Collins M. Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant. Br J Sports Med 43: 352–356, 2009.
65. Posthumus M, September AV, O'Cuinneagain D, van der Merwe W, Schwellnus MP, Collins M. The association between the COL12A1 gene and anterior cruciate ligament ruptures. Br J Sports Med 44: 1160–1165, 2010.
66. Potthoff MJ, Wu H, Arnold MA, Shelton JM, Backs J, McAnally J, Richardson JA, Bassel-Duby R, Olson EN. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest 117: 2459–2467, 2007.
67. Precision Medicine Initiative Working Group Precision. Report to the Advisory Committee to the Director: The Precision Medicine Initiative Cohort Program—Building a Research Foundation for 21st Century Medicine. Washington, DC: National Institutes of Health, 2015.
68. Reynard LN, Bui C, Canty-Laird EG, Young DA, Loughlin J. Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Hum Mol Genet 20: 3450–3460, 2011.
69. Riiser A. The human microbiome, asthma, and allergy. Allergy Asthma Clin Immunol 11: 1, 2015.
70. Robson-Ansley PJ, Blannin A, Gleeson M. Elevated plasma interleukin-6 levels in trained male triathletes following an acute period of intense interval training. Eur J Appl Physiol 99: 353–360, 2007.
71. Robson-Ansley PJ, Milander Ld, Collins M, Noakes TD. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol 29: 411–418, 2004.
72. Rokavec M, Öner MG, Hermeking H. lnflammation-induced epigenetic switches in cancer. Cell Mol Life Sci 73: 23–39, 2016.
73. Sánchez-Martín A, García-Sánchez A, Isidoro-García M. Review on pharmacogenetics and pharmacogenomics applied to the study of asthma. Methods Mol Biol 1434: 255–272, 2016.
74. September A, Posthumus M, Collins M. Application of genomics in the prevention, treatment and management of Achilles tendinopathy and anterior cruciate ligament ruptures. Recent Pat DNA Gene Seq 6: 216–223, 2012.
75. September A, Posthumus M, Van der Merwe L, Schwellnus M, Noakes T, Collins M. The COL12A1 and COL14A1 genes and Achilles tendon injuries. Int J Sports Med 29: 257–263, 2008.
76. Seto JT, Lek M, Quinlan KG, Houweling PJ, Zheng XF, Garton F, MacArthur DG, Raftery JM, Garvey SM, Hauser MA. Deficiency of α-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling. Hum Mol Genet 20: 2914–2927, 2011.
77. Seto JT, Quinlan KG, Lek M, Zheng XF, Garton F, MacArthur DG, Hogarth MW, Houweling PJ, Gregorevic P, Turner N. ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. J Clin Invest 123: 4255–4263, 2013.
78. Stenvinkel P, Karimi M, Johansson S, Axelsson J, Suliman M, Lindholm B, Heimbürger O, Barany P, Alvestrand A, Nordfors L. Impact of inflammation on epigenetic DNA methylation—A novel risk factor for cardiovascular disease? J Intern Med 261: 488–499, 2007.
79. Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord 16: 55–65, 2015.
80. Tam WL, Weinberg RA. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med 19: 1438–1449, 2013.
81. Thomas T, Gilbert J, Meyer F. Metagenomics-a guide from sampling to data analysis. Microb Inform Exp 2: 1, 2012.
82. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett C, Knight R, Gordon JI. The human microbiome project: Exploring the microbial part of ourselves in a changing world. Nature 449: 804, 2007.
83. Vincent B, Windelinckx A, Nielens H, Ramaekers M, Van Leemputte M, Hespel P, Thomis MA. Protective role of α-actinin-3 in the response to an acute eccentric exercise bout. J Appl Physiol (1985) 109: 564–573, 2010.
84. Virgin HW, Todd JA. Metagenomics and personalized medicine. Cell 147: 44–56, 2011.
85. Vuorio E, De Crombrugghe B. The family of collagen genes. Annu Rev Biochem 59: 837–872, 1990.
86. Waterland RA. Epigenetic mechanisms and gastrointestinal development. J Pediatr 149: S137–S142, 2006.
87. Webster LR, Belfer I. Pharmacogenetics and personalized medicine in pain management. Clin Lab Med 36: 493–506, 2016.
88. Wood M, Gibbons SM, Lax S, Eshoo-Anton TW, Owens SM, Kennedy S, Gilbert JA, Hampton-Marcell JT. Athletic equipment microbiota are shaped by interactions with human skin. Microbiome 3: 1, 2015.
89. You H, Ding W, Rountree CB. Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-β. Hepatology 51: 1635–1644, 2010.
90. Zhang Q, Cox M, Liang Z, Brinkmann F, Cardenas PA, Duff R, Bhavsar P, Cookson W, Moffatt M, Chung KF. Airway microbiota in severe asthma and relationship to asthma severity and phenotypes. PLoS One 11: e0152724, 2016.

genetics; epigenetics; gene expression; pharmacogenomics; metagenomics

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