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Genetic Inheritance Effects on Enduranceand Muscle StrengthAn Update

Aldo M. Costa,1,2 Luiza Breitenfeld,3,4 Antonio J. Silva,2,5 Ana Pereira,2,5 Mikel Izquierdo6

and Mario C. Marques1,2

1 Department of Sport Sciences at the University of Beira Interior, Covilha, Portugal

2 Centre for Research in Sport, Health and Human Development, Vila Real, Portugal

3 Faculty of Health Sciences at the University of Beira Interior, Covilha, Portugal

4 Research Centre for Health Sciences, Covilha, Portugal

5 Department of Sport Science, Exercise and Health at the University of Tras-os-Montes and Alto Douro,

Vila Real, Portugal

6 Department of Health Sciences, Public University of Navarre, Navarre, Spain

Abstract Top-level sport seems to play a natural Darwinian stage. The most out-standing athletes appear to emerge as a result of exogenous influences ofnature and/or coincidence, namely, the contingency of practicing certainsport for which their talents best fit. This coincidence arises because certainindividuals possess anatomical, metabolic, functional and behavioural char-acteristics that are precisely those required to excel in a given sport. Apartfrom the effects of training, there is strong evidence of genetic influence uponathletic performance. This article reviews the current state of knowledge re-garding heritable genetic effects upon endurance and muscle strength, as re-ported by several twin and family studies. Due, probably, to the inaccuracy ofthe measurement procedures and sampling error, heritability estimates differwidely between studies. Even so, the genetic inheritence effects seem incon-trovertible in most physical traits: ~40–70% for peak oxygen uptake and car-diac mass and structure, and ~30–90% for anaerobic power and capacity,ranging according to the metabolic category. Studies in development by sev-eral researchers at this present time seem to guarantee that future reviews willinclude twins and family studies concerning genes associated with the adaptiveprocesses against hormetic agents, such as exercise, heat and oxidative stress.

1. Introduction

The expression of a gene is a dynamic processmodulated by neural and hormonal mechanismsactivated by growth needs and environmentalparticularities, as well as other requirements ofcellular regulation.[1] Thus, the study of pheno-

type variation and its response to different en-vironmental interactions allows us to assess therole of genes. The heredity factor, for example, ina specific physical domain can be estimated byanalysing the degree of similarity between closelyrelated individuals, compared with other geneti-cally distant subjects.

LEADING ARTICLESports Med 2012; 42 (6): 449-458

0112-1642/12/0006-0449/$49.95/0

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In the context of physical performance, thedeterminants of phenotypic variation are still notfully known (i.e. age, sex or conditions of training,along with others, have important roles). Addi-tionally, social learning and parental role model-ling are relevant factors in explaining familialsimilarity and familial aggregation in patterns ofsedentary and physically active behaviour.[2-5]

Hence, the model proposed by Bouchard et al.[6]

is now widely accepted and shows physicalactivity and sports performance as an entirephenotype influenced by a complex, hypotheticalmultifactorial scenario. As such, human physicalperformance, like any other individual character-istic, is dependent on interactions between genesand environment.[7] However, various scientificstudies suggest a significant effect of genetics onathletic performance, even when adjusted for themanifest effect of the environment.[8,9] Indeed,relevant traits, such as aerobic power, explosivestrength or anaerobic capacity have been reportedby several studies as parameters of high herit-ability.[10-12] For measures such as upper bodystrength, the variability within the population ishigher than the improvements to be expectedfrom an optimal training programme.[13,14]

Recently, Buxens et al.[15] found that 21.4% ofgenetic factors contribute to sports performance.In this context, knowing which genetic profilecontributes most to athletic performance is nowbecoming the main focus. Due to the fact that theathletic status phenotype is a complex trait, it islikely the effect of single gene variant is small.[16]

Ruiz et al.,[17] for example, have identified a poly-genic profile that distinguishes elite power fromendurance athletes and nonathletic population.However, the proportion of each gene variant inexplaining the variance of a complex trait such asthis is totally unknown. From our point of view,some challenging ethical dilemmas will likelyarise very soon, such as genetic testing for athletictalent or even the modification of the humangenome.

Despite all this, the phenotypic expression ofa hereditary factor precedes the study of thepolymorphic variation. Although an individual’spotential for excelling in endurance or powersports can be partly predicted based on specific

and/or complex gene-gene interactions, environ-mental factors and epigenetic mechanisms arealso important contributors of being an athleticchampion.[15,18,19]

In brief, the purpose of this article is to providea balanced review of the literature concerningthe relative contributions of genetic and environ-mental factors to sports performance traits suchas aerobic endurance, muscular strength and power.Using keywords, a comprehensive search was con-ducted on MEDLINE and SPORTDiscus� data-bases. Only twins and family data-based studies inpeer-reviewed journals were included.

2. Genetic Inheritance Effects onAerobic Endurance

The hereditable factor in aerobic endurancehas commonly been ascertained by a classical twinmodel study on a single period of assessment. How-ever, a wide diversity in sample size and differentphenotype measurement procedures may be no-ticed, which often leads to conflicting results.

As is common knowledge, the maximal oxy-gen uptake (

.VO2max) parameter is the result of the

joint efficiency of the cardiovascular, respiratoryand musculoskeletal systems; together they de-termine a particular ability to capture, transportand use oxygen. Early studies on the role of he-redity in the variability of the

.VO2max indicate the

almost unconditional influence of genetics in thisparameter.[20,21] Other twin studies confirmed astrong genetic influence, although results showed aconsiderably lower contribution (table I).[13,22,23,28-30]

The first genetic studies of.VO2max based on

family data,[31,32] also suggested a significant in-heritance component (about 40%). More recentfamily studies[24,26] suggest that genetic factorscould account for about 50% of the variance inthis parameter (table I). According to Bouchardet al.,[24] the maternal influences reach about 30%,in part potentially associated with mitochondrialinheritance. The trainability of

.VO2max is also

highly familiar and includes a significant geneticcomponent.[25] The study of genetic inheritanceeffects on submaximal aerobic fitness is also note-worthy; although, as yet, the scientific evidenceis scarce. The study of Gaskill et al.,[27] using

450 Costa et al.

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familial data from the HERITAGE Family Study,is one of the few recognized contributions to thisarea. The authors used the oxygen uptake (

.VO2)

[mL�min-1] at the ventilatory threshold (adjustedfor body weight) as a valid parameter to estimatesubmaximal sustainable aerobic work capacityand aerobic fitness. Results show maximal heri-tability effects of 58% and 54% in samples forWhite and Black subjects, respectively. However,the response of this submaximal parameter totraining appears characterized by apparently di-vergent familial components (22% and 51%) inWhite and Black subjects, respectively. Accord-ing to the authors, the familial effect for ventila-tory threshold/

.VO2max in Black subjects appeared

to be accounted for by fat and fat-free mass. Thisstudy underlines an important and controversialissue in subject recruitment for human geneticsstudies – race and ethnicity, as a classifying vari-able. In one perspective, race by definition is notan inherently biological trait (but rather a socialconstruct), and also an imperfect means of de-termining geographic ancestry.[33] On the flip sideof the controversy, scientists argue that geneticdifferences do exist among the various popula-

tions. Geographic ancestry could influence somegenetic and physiological traits and this couldindicate that the distribution exhibits clear di-versity between different ethnic groups. In con-sequence, geographic ancestry variation couldexplain some of the non-consensual results thatare present in the literature.

Because there is no consensus regarding thisissue, future studies should at least consider thecollection of information about ethnicity whenrecruiting subjects.

With regard to the cardiovascular system,trained athletes generally have higher rates ofventricular mass, stroke volume, cardiac output,bradycardia and lower resting heart rate underconditions of submaximal exercise.[6] Regardingthis, genetic heritage is clearly evident in the struc-ture, mass and function of heart muscle (table II),resulting in a hereditary influence of 29–83%[34-40]

depending on the ethnicity of subjects. Moreover,this large range of heritability values is also de-pendent on the measurement accuracy of pheno-types; cardiac magnetic resonance[40] is superiorto echocardiography for quantitatively imagingthe heart.

Table I. Heritability estimates of aerobic performance (family and twin studies)

Study (year) Subjects Parameter Heritability estimates

Bouchard et al.[22]

(1986)

172 young adult twins.VO2peak

40% (p > 0.05)

Fagard et al.[23]

(1991)


68% (p < 0.001)

40% (p = 0.05) after weight adjustment

26% (p > 0.05) after life-style factors

adjustment

Maes et al.[13] (1996) 105 young child twins.VO2peak

65% (p < 0.05)

Bouchard et al.[24]

(1998)

429 sedentary adult individuals from

86 families

.VO2peak

50% (p < 0.05)

Bouchard et al.[25]

(1999)

481 adults from 98 two-generation

familiesResponse of

.VO2peak to

training

47% (p < 0.05) adjusted for age and

sex

Perusse et al.[26]

(2001)

483 individuals from two-generation

families (184 parents and 299 biological

offspring)

.VO2 at 50 W, 60% and 80%.VO2max

48–74% (p < 0.05) for baseline

phenotypes

23–57% (p < 0.05) for the training

response phenotypes

Gaskill et al.[27]

(2011)

199 nuclear families (100 White and

99 Black)

.VO2 at the ventilatory threshold 58% (p < 0.05) in White and 54%

(p < 0.05) in Black families

(adjusted for weight, age, fat mass and

fat-free mass)

Mustelin et al.[28]

(2011)


71% (p < 0.05), after weight adjustment

.VO2 = oxygen uptake;

.VO2max = maximal

.VO2;

.VO2peak = peak

.VO2.

Endurance and Muscle Strength Genetic Inheritance Effects 451


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With regard to cardiac dimension differencesbetween athletes and non-athletes, the few studiespublished[41,42] suggest that no significant geneticcomponent seems to exist (at least in resting state).This could mean that cardiac factors are not sig-nificantly involved in the inheritance of aerobicpower but are instead due to inheritance of othercardiac features, which are only expressed duringexercise.[41,43] Further studies are needed to betterunderstand the inheritance of the qualities char-acteristic of an athlete’s heart during exertion.

Regarding pulmonary function, while the con-textual determinants associated with lung functionhave been extensively studied, genetic influencehas only recently been given more attention.[44,45]

Chen[44] compiled some of the most relevant twinand family studies about pulmonary function. Asthese authors affirm, espirometric measures oflung function are heritable traits that reflect res-piratory health and predict morbidity and mor-tality. One of the measures is the forced expiratoryvolume during one second (FEV1.0) – on thisparameter, the genetic inheritance effects rangebetween 28%[46] and 47%.[47] Additionally, stud-ies in monozygotic twins have consolidated theevidence of genetic contribution to lung functionvariability, although with broad-spectrum esti-mates. Hubert et al.,[48] who studied 127 mono-zygotic twins and 141 dizygotic twins, estimateda hereditary influence of 77% for FEV1.0. In astudy of 256 monozygotic twins and 158 dizygot-ic twins, Redline et al.[49] suggested that 40–75%of the lung function variability is due to geneticinheritance. Curiously, Ghio et al.[50] found nostatistical significance of genetic contributionwithin this parameter; however, it must be em-phasized that the small sample studied may ex-plain part of the contradictory results achieved(74 twins). The strong genetic influence in pul-monary function phenotypes has recently beenconfirmed by genetic polymorphism studies,[51]

genome-wide association studies[52,53] and evenmeta-analyses approaches.[54]

Although lung function does not appear tobear upon sports performance, there are somerelevant studies on the ventilatory response incase of hypoxia,[55,56] suggesting a hereditary in-fluence on physiological processes of adaptation

to high-altitude environments.[57,58] Moreover,the large intervariability of blood markers in eliteathletes in response to acute hypoxic exposure,corroborating previous observations made in otherpopulations, would seem to suggest a significantgenetic inheritance.[55,59] Nevertheless, repeatedshort episodes of reduced oxygenation alone or incombination with intense endurance work is nowunderstood to sustain exercise performance whenatmospheric oxygen levels are low. Genome-mediated muscle plasticity is then controlledby feedback through constraints of the oxygenpathway.[56]

3. Heredity in Anaerobic Power andCapacity

The differences in the ability to perform anaer-obic motor tasks are due to several factors, in-cluding age, sex, metabolic capacity, muscle mass,higher muscle fibre recruitment and greater den-sity of fast fibres.[60] A classic example of thisvariation occurs among athletes of different sports’specialties (e.g. sprinters vs distance runners), asresult of the specific effect of training.[61] For ex-ample, differences in properties of isolated slow-twitch (ST) and fast-twitch (FT) muscle fibresand motor units have been well documented. Theendurance capacity has been related to ST-fibrepredominance (50%) whereas FT fibres are re-lated to power and speed capacity. Consistentwith this evidence, power athletes and sprinterstend to have higher proportions of FT muscle fi-bres with low-oxidative capacity when comparedwith endurance athletes, plus higher percentagesof ST muscle fibres.[62-64] Nevertheless, it hasbeen widely suggested that muscle function isalso markedly influenced by genetic factors.[65,66]

As such, current research has not yet clarifiedwhether this variability is largely environmental orgenetic in origin or even the result of gene-traininginteraction.

In substance, the functioning of human skele-tal muscle under anaerobic conditions requiresanalysis in at least three distinct metabolic cate-gories: maximal anaerobic work and/or explosivetasks; maximal tasks of short duration; and long-term maximal anaerobic tasks.[60]

452 Costa et al.


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3.1 Anaerobic and Explosive Tasks

The literature on this subject reports a con-siderable influence of heredity in muscle functionduring anaerobic or explosive tasks, althoughthere is a disparity in obtained results, whichsuggests that these traits should be furtherinvestigated.

With regard to eccentric force of elbow flexors,Thomis et al.[67] reported a genetic explanation of65% to 77%. For maximum strength in leg ex-tension, the genetic contribution was estimated at46% by Arden and Spector[68] and, later, at 42%by Zhai et al.[69] For maximum strength in armflexion, the genetic role was estimated at 77% byThomis et al.[67] and subsequently from 30% to80% by Thomis and colleagues,[70] depending onthe angle, type and contraction speed performed.According to Thomis and colleagues,[70] the im-portance of genetic factors in eccentric arm flexorstrength (62–82%) would seem larger than forconcentric flexion (29–65%), and therefore thesemay suggest that heritability estimation followedthe torque-velocity curve contributing differentlyto eccentric and concentric torques. Further-more, the genetic contribution for static strengthseems quite high: 69%[67] to 72%.[13] For isometrichandgrip strength, the inheritance element islower but remains a significant component, witha contribution of 30%.[68] With regard to max-imal isometric quadriceps strength, the study ofJones and Klissouras[71] reports a substantialhereditary coefficient of 0.83. However, it is in-teresting that Komi and Karlsson[72] have re-pudiated the existence of any significant influenceof genetics in this phenotype.

In the elderly, the decline in muscle strengthand power suggests that there may be changes inthe relative contributions of genetic and environ-mental effects. New specific environmental effectscould be due to the onset of new disease processesor changes in lifestyle.[73] Nevertheless, the con-tribution of genetic effects to muscle strengthseems to remain significant for measures such asisometric muscle strength[12,73,74] or leg extensorpower.[73] Unfortunately, very few longitudinalstudies of elderly people have been conductedand further evidence must be accumulated.T

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3.2 Short-Duration Anaerobic Tasks

The literature suggests that the genetic con-tribution in short-duration motor tasks is quitesignificant. The pioneering study by Komi andcolleagues[75] reports an intraclass correlationcoefficient (ICC) of 0.58 and 0.80 for mono-zygotic and dizygotic twins, respectively. Ad-ditionally, the dizygotic twins showed a highervariance (5-fold higher) between twin pairs. Forinstance, Simoneau et al.[76] involved a largesample of subjects (a total of 328 individuals) whowere intensively studied for anaerobic capacityon a cycle ergometer. Surprisingly, the resultswere convergent with previous studies, suggestingthat the fact of sharing ‘half of the genome’ and‘living together’ translates into greater intraclasssimilarity than that seen in individuals who ‘livetogether’ but do not have genes in common. Thisis a variation on the typical twin study, whichprovides important insight into the role of geneticversus environmental factors. Studies with com-binations of family members can even extendbeyond the use of twin pairs.[77] This approachshould be considered for future replication studies.

Meanwhile, the classical twin study byWolanskiet al.[77] is an important reference, since it reportshigh heritability estimates for several phenotypes,such as handgrip strength and running speed(20m, 30m and 60m). It is interesting to notethat the inheritance effect seems to decrease asthe duration of the event increases. The study ofCalvo et al.,[11] with 32 Caucasian male twinssubjected to various conventional anaerobic as-sessments, shows a significant hereditability in-dex of 0.74 for maximum strength at 5 seconds inthe Wingate test. The study of Missitzi et al.[78]

should be also be noted because it suggests astrong genetic effect for neuromuscular coordina-tion in fast movements, reporting an ICC of 0.85and 0.73 for monozygotic and dizygotic twins,respectively.

3.3 Long-Term Anaerobic Tasks

Concerning the heritability of lactic acid con-centrations after exercise, the literature remainssparse and quite divergent. Komi and Karlson[72]

and Prud’homme et al.[29] disclaim any influenceof genetics in this metabolic parameter. Actually,one of the few conclusive studies on this matterwas published by Calvo et al.,[11] who reportedsignificant hereditability indexes in maximal lac-tate concentration (0.82) and lactate concentra-tion (0.84), as well as in the second (0.93) andthird minute (0.92) of recovery after the deficit test.More recently, Maridaki[79] adds that the matura-tion of anaerobic metabolism and neuromuscularactivation seem to induce some variation to theheritability of lactic acid concentrations (here-ditability index of 0.98 for pre-adolescents and of0.73 for adolescents, p< 0.05). Regarding this, theinformation concerning genetic inheritance ef-fects on long-duration anaerobic tasks (up to 90seconds) seems both conflicting and scarce. Re-sults here indicated a marked genetic influence inthe 1000m run performance, as the ICCs were0.98 and 0.69 for monozygotic and dizygotictwins, respectively. In a previous study, the sameauthor[20] had already studied the hereditary in-fluence on maximum lactate accumulation, re-porting an ICC of 0.93 for monozygotic twinsand of 0.76 for dizygotic twins. These claims werelater supported by Calvo et al.,[11] who showed asignificant heritability index (0.84; p< 0.05) fortotal power in a 30 seconds Wingate test. Never-theless, the literature seems to suggest a significantgenetic influence, although there are conflictingresults that should clarified by further studies.

3.4 Other Determinants of AnaerobicPerformance

It should be mentioned that skeletal muscle isthe largest component of adipose tissue-free bodymass in humans. As such, we may assume that thehigh heritability of lean body mass[11] will be ex-tended to skeletal muscle mass. The few studieson this issue have shown that skeletal muscle massappears, in fact, a heritable phenotype. Looset al.[80] reported that the circumference varianceof the upper arm and calf (87–95%) is due toheredity. A study by Sanchez-Andres and Mesa[81]

reports, for various anthropometric and body com-position parameters, a significant hereditabilityindex: 0.68 for the perimeter of the forearm, 0.58

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for the circumference of the thigh and 0.67 for theperimeter of the calf. Thomis et al.[70] also observeda very high genetic influence for anthropometricand arm cross-sectional areameasurements (>85%),adding that common environmental factors areonly significant for anthropometrically estimatedmid-arm muscle tissue (48%).

Some studies also suggest the significant roleof genetics in the distribution of muscle fibretypes. One of the first studies was published byKomi et al.[82] and was based on a small sample ofmonozygotic (15 pairs) and dizygotic (16 pairs)twins. The results showed a surprising heredit-ability index (p < 0.05) for the proportion of typeI fibres: 0.99 in men and 0.93 in women. Thesedata suggest that the ratio of muscle fibre type isalmost exclusively dependent on genes. However,these data should be treated with caution due tothe very small sample (31 pairs). Indeed, declar-ing a difference or a significant effect that doesnot exist in reality is one of the consequences ofan inadequate level of statistical power. In addi-tion, it should be noted that about 15% of thetotal variance in the proportion of type I musclefibres could be explained by the error associatedwith muscle sampling and technical variance.[83]

This means that the hereditability index of fibre-type ratio reported by the literature must beviewed with discretion. In fact, Bouchard et al.[22]

suggests no significant genetic effect for musclefibre types I, IIa and IIb distribution and fibreareas. Instead, according to the authors, geneticfactors appear to be involved in the variation ofregulatory enzymes of the glycolytic and citricacid cycle pathways, and in the variation of theoxidative to glycolytic activity ratio. Furthermore,there is also evidence of heredity in adaptation totraining with regard to enzymatic activity asso-ciated with muscle contraction.[84,85]

The literature is limited regarding the quanti-fication of genetic and environmental factorsin muscular strength adaptations. According toThomis et al.,[67] there would seem to be a highpleiotropic gene action (20–77%) and a minoractivation of training specific genes during strengthtraining (20%). However, the genetic regulationduring adolescence appears to be a factor im-portant enough to be a main cause of the ob-

served phenotypic stability in vertical jump per-formance.[86] The heritability and environmentalcontributions to skeletal muscle phenotypes maydiffer as a function of sex and age, at least inmultigenerational families of African heritage.[87]

Rationally, we can expect that the younger thesubjects studied, the higher will be the hereditaryinfluence and, by consequence, the lower the en-vironment effect. Furthermore, it seems that thedifferential acute response among muscle fibretypes may also play a critical role in the sub-sequent adaptations and, for that reason, in her-itability studies.[1] According to these authors’results, basal gene expression has been shown tobe variable among fibre types, which may influ-ence the response and eventual adaptations to anexercise stimulus. Therefore, it seems logical toexpect that the hereditary influence will vary,depending also on the subject’s physical activitylevel. This is another important issue that war-rants consideration in future studies.

4. Conclusions

The sources of phenotype variability arise fromthree major factors: experimental errors, environ-ment stimuli and genetic factors. The environmentstimuli interact with common genetic variantsto determine individual characteristics includingphysical performance. Thus, the study of geneticinheritance effects allows for estimation of thegenetic contribution to total variance. However,the literature estimation of this genetic contribu-tion is, to date, very uneven among studies, whichprecludes the drawing of any exact conclusions.These differences are a consequence of differentphenotype evaluation procedures beyond the ex-perimental error associated with each measure-ment. Furthermore, the age, sex and ethnicity ofstudied subjects are other important factors thatappear to contribute to the divergent results. Theeffect of different environmental circumstanceson the relative contribution of genes is equallyimportant. Indeed, gene expression can vary inresponse to changing environments, as well asin number and the epistasis processes involved.Since most studies did not report any effect size,future research should therefore focus on achieving



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adequate statistical power. There is also a needfor replication studies using improved measure-ment precision of phenotypes and a more homo-geneous social environment shared across thestudy population (e.g. physical fitness levels).

In summary, there is an obvious multifactorialcausation for the inexact nature of measuringinheritance in complex traits. Here, family studiesprovide more information that is precise for al-leles that are shared identically by descent. Morecomplex analysis of families is possible (trans-mission disequilibrium test and the sibship dis-equilibrium test), but the use of actual DNAsequence variation data is required. Future modelsthat take into account the association betweenathletic status and complex gene-gene and gene-environment interactions will have to be studiedon the Hormetic Theory base. This approach rep-resents the biphasic dose-response patterns totoxic challenges[1] by exposure to hormetic agentsat threshold levels (e.g. exercise, heat and oxida-tive stress).

Acknowledgements

No sources of funding were used to assist in the prepara-tion of this review. The authors have no conflicts of interestthat are directly relevant to the content of this review.

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Correspondence: Dr Mikel Izquierdo, Department of HealthSciences, Public University of Navarre, Spain. Campus ofTudela, Av. de Tarazona s/n, 31500 Tudela, Navarre, Spain.E-mail: [email protected]

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