Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive and Accurate Assessment of the Zygosity of Adult Twins.

Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.

Age differences in genetic and environmental variations in stress-coping during adulthood: a study of female twins.

The way people cope with stressors of day to day living has an important influence on health. The aim of the present study was to explore whether genetic and environmental variations in stress-coping differ over time during adulthood. The brief COPE was mailed to a large sample of the UK female twins (N = 4,736) having a wide range of age (20-87 years). Factor analyses of the items of the brief COPE yielded three coping scales: 'Problem-Solving', 'Support Seeking', and 'Avoidance'. Monozygotic and dizygotic twin correlations tended to become lower with age for all three scales, suggesting that unique environmental factors may become more important with age during adulthood. Model-fitting results showed that relative influences of unique environmental factors increased from 60 % at age 20 years to 74% at age 87 years for 'Problem-Solving' and 56 % at age 20 years to 76% at age 87 years for 'Avoidance'. During the same age period, genetic factors decreased from 40 to 26 % for 'Problem-Solving' and from 44 to 24 % for 'Avoidance'. For 'Seeking Support', the magnitude of genetic and unique environmental factors was not significantly different across the adulthood. For all three scales, shared environmental effects were negligible. Overall, our findings implicate that the effects of environment that stem from idiosyncratic experience of stressful life events accumulate and become increasingly important in adulthood.

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Evidence for a genetic overlap between body dysmorphic concerns and obsessive-compulsive symptoms in an adult female community twin sample.

Body dysmorphic disorder (BDD) is thought to be etiologically related to obsessive-compulsive disorder (OCD) but the available evidence is incomplete. The current study examined the genetic and environmental sources of covariance between body dysmorphic and obsessive-compulsive symptoms in a community sample of adult twins. A total of 2,148 female twins (1,074 pairs) completed valid and reliable measures of body dysmorphic concerns and obsessive-compulsive symptoms. The data were analyzed using bivariate twin modeling methods and the statistical programme Mx. In the best-fitting model, the covariation between body dysmorphic and obsessive-compulsive traits was largely accounted for by genetic influences common to both phenotypes (64%; 95% CI: 0.50-0.80). This genetic overlap was even higher when specific obsessive-compulsive symptom dimensions were considered, with up to 82% of the phenotypic correlation between the obsessing and symmetry/ordering symptom dimensions and dysmorphic concerns being attributable to common genetic factors. Unique environmental factors, although influencing these traits individually, did not substantially contribute to their covariation. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance. The association between body dysmorphic concerns and obsessive-compulsive symptoms is largely explained by shared genetic factors. Environmental risk factors were largely unique to each phenotype. These results support current recommendations to group BDD together with OCD in the same DSM-5 chapter, although comparison with other phenotypes such as somatoform disorders and social phobia is needed.

Prevalence and heritability of skin picking in an adult community sample: a twin study.

Skin-picking disorder (SPD) is a disabling psychiatric condition that can lead to skin damage and other medical complications. Epidemiological data is scarce and its causes are unknown. The present study examined the prevalence and heritability of skin-picking symptoms in a large sample of twins. A total of 2,518 twins completed a valid and reliable self-report measure of skin-picking behavior. The prevalence of clinically significant skin picking was established using empirically derived cut-offs. Twin modeling methods were employed to decompose the variance in the liability to skin picking into additive genetic and shared and non-shared environmental factors. A total of 1.2% of twins scored above the cut-off, indicative of clinically significant skin picking. All these participants were women. Univariate model-fitting analyses (female twins only, N = 2,191) showed that genetic factors accounted for approximately 40% (95% CI 19-58%) of the variance in skin picking, with non-shared environmental factors and measurement error accounting for the remaining variance (60% [95% CI 42-81%]). Shared environmental factors were negligible. It is concluded that pathological skin picking is relatively prevalent problem, particularly among women, and that it tends to run in families primarily due to genetic factors. Non-shared environmental factors are also likely to play an important role in its etiology.

Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits.

Eating disorders (EDs) are common, complex psychiatric disorders thought to be caused by both genetic and environmental factors. They share many symptoms, behaviors, and personality traits, which may have overlapping heritability. The aim of the present study is to perform a genome-wide association scan (GWAS) of six ED phenotypes comprising three symptom traits from the Eating Disorders Inventory 2 [Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia], Weight Fluctuation symptom, Breakfast Skipping behavior and Childhood Obsessive-Compulsive Personality Disorder trait (CHIRP). Investigated traits were derived from standardized self-report questionnaires completed by the TwinsUK population-based cohort. We tested 283,744 directly typed SNPs across six phenotypes of interest in the TwinsUK discovery dataset and followed-up signals from various strata using a two-stage replication strategy in two independent cohorts of European ancestry. We meta-analyzed a total of 2,698 individuals for DT, 2,680 for BD, 2,789 (821 cases/1,968 controls) for Bulimia, 1,360 (633 cases/727 controls) for Childhood Obsessive-Compulsive Personality Disorder trait, 2,773 (761 cases/2,012 controls) for Breakfast Skipping, and 2,967 (798 cases/2,169 controls) for Weight Fluctuation symptom. In this GWAS analysis of six ED-related phenotypes, we detected association of eight genetic variants with P < 10(-5) . Genetic variants that showed suggestive evidence of association were previously associated with several psychiatric disorders and ED-related phenotypes. Our study indicates that larger-scale collaborative studies will be needed to achieve the necessary power to detect loci underlying ED-related traits.

A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.

Psychiatric disorders such as schizophrenia are commonly accompanied by cognitive impairments that are treatment resistant and crucial to functional outcome. There has been great interest in studying cognitive measures as endophenotypes for psychiatric disorders, with the hope that their genetic basis will be clearer. To investigate this, we performed a genome-wide association study involving 11 cognitive phenotypes from the Cambridge Neuropsychological Test Automated Battery. We showed these measures to be heritable by comparing the correlation in 100 monozygotic and 100 dizygotic twin pairs. The full battery was tested in approximately 750 subjects, and for spatial and verbal recognition memory, we investigated a further 500 individuals to search for smaller genetic effects. We were unable to find any genome-wide significant associations with either SNPs or common copy number variants. Nor could we formally replicate any polymorphism that has been previously associated with cognition, although we found a weak signal of lower than expected P-values for variants in a set of 10 candidate genes. We additionally investigated SNPs in genomic loci that have been shown to harbor rare variants that associate with neuropsychiatric disorders, to see if they showed any suggestion of association when considered as a separate set. Only NRXN1 showed evidence of significant association with cognition. These results suggest that common genetic variation does not strongly influence cognition in healthy subjects and that cognitive measures do not represent a more tractable genetic trait than clinical endpoints such as schizophrenia. We discuss a possible role for rare variation in cognitive genomics.

Variance components models for physical activity with age as modifier: a comparative twin study in seven countries.

Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self-reported data from twins aged 19 to 50 from seven countries that collaborated in the GenomEUtwin project: Australia, Denmark, Finland, Norway, Netherlands, Sweden and United Kingdom. Results confirmed the importance of genetic influences on physical activity in all countries and showed an age-related decrease in heritability for 4 countries. In the other three countries age did not interact with heritability but those samples were smaller or had a more restricted age range. Effects of shared environment were absent, except in older Swedish participants. The study confirms the importance of taking age effects into account when exploring the genetic and environmental contribution to physical activity. It also suggests that the power of genome-wide association studies to identify the genetic variants contributing to physical activity may be larger in young adult cohorts.

Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

Cerebellar asymmetry in a pair of monozygotic handedness-discordant twins.

Increasing evidence for a cerebellar role in human cognition has accrued with respect to anatomically and functionally distinct lobules. Questions of laterality, however, have been largely overlooked. This study therefore introduced and applied a novel measurement protocol for comparatively bias-free analysis of cerebellar asymmetries. Volumetric measurements were performed on magnetic resonance images from a single pair of monozygotic handedness-discordant twins. Against a background of functional cortical asymmetry for verbal and visuo-spatial functional magnetic resonance imaging activation, which was mirrored in the left-handed twin (Lux et al. 2008), between-twin differences in cerebellar asymmetry are described. Interestingly, asymmetry measures for the whole cerebellum did not correspond to either the direction of hand preference or to the weaker (functional magnetic resonance imaging) lateralization of the left-handed twin. The twins both showed clockwise cerebellar torques. This mirrored a counter-clockwise cerebral torque in the right-handed twin only. Selected single cerebellar lobules V and VII displayed between-twin laterality differences that partially reflected their discrepant handedness. Whole cerebellum anatomical measures appeared to be unrelated to single functional cortical asymmetries. These analyses contribute further anatomical evidence pertaining to the existence of multiple structurally and functionally distinct cortico-cerebellar networks of the healthy human brain in vivo.

Replication of psychometric properties of the FSFI and validation of a modified version (FSFI-LL) assessing lifelong sexual function in an unselected sample of females.

INTRODUCTION: The 19-item Female Sexual Function Index (FSFI) is an easy-to-administer self-report questionnaire, allowing multidimensional assessment of female sexual function and female sexual dysfunction (FSD) over the past 4 weeks. However, studies aiming to dissect the underlying pathoetiology-especially biophysiological factors-often require assessment of sexual function over a broader time frame. AIM: The purpose of this study was to develop a modified version of the widely used FSFI which allows assessment of women's lifelong sexual function-the FSFI-LL-and to evaluate the psychometric properties and aptness of this new version. METHODS: A total of 1,589 unselected female twins from the TwinsUK registry completed both original and new versions of the FSFI. After applying exclusion criteria, 1,489 women were eligible for this study. MAIN OUTCOME MEASURE: Reliability was tested using Cronbach's alpha coefficient. Construct validity was evaluated by exploratory factor analysis and confirmatory factor analysis (CFA). Domain response differences between the original FSFI and the FSFI-LL were assessed using unpaired t-tests. RESULTS: The modified FSFI-LL showed adequate internal consistency reliabilities for all six dimensions and the total score (Cronbach's α = 0.79 - 0.92). Principal component analysis resulted in a best fitting five-factor solution. CFA confirmed the underlying domain structure to be same as for the FSFI, supporting the factorial validity of the modified questionnaire. In addition, successful replication of the psychometric properties of the original FSFI was demonstrated. CONCLUSIONS: The results provide evidence of good reliability and validity of the FSFI-LL. This modified version therefore represents a suitable tool for screening lifelong sexual function in women and can be applied in trials investigating etiological factors contributing to more enduring patterns of FSD.

Genetic and environmental influences on self-reported G-spots in women: a twin study.

INTRODUCTION: There is an ongoing debate around the existence of the G-spot--an allegedly highly sensitive area on the anterior wall of the human vagina. The existence of the G-spot seems to be widely accepted among women, despite the failure of numerous behavioral, anatomical, and biochemical studies to prove its existence. Heritability has been demonstrated in all other genuine anatomical traits studied so far. AIM: To investigate whether the self-reported G-spot has an underlying genetic basis. METHODS: 1804 unselected female twins aged 22-83 completed a questionnaire that included questions about female sexuality and asked about the presence or absence of a G-spot. The relative contribution of genetic and environmental factors to variation in the reported existence of a G-spot was assessed using a variance components model fitting approach. MAIN OUTCOME MEASURES: Genetic variance component analysis of self-reported G-spot. RESULTS: We found 56% of women reported having a G-spot. The prevalence decreased with age. Variance component analyses revealed that variation in G-spot reported frequency is almost entirely a result of individual experiences and random measurement error (>89%) with no detectable genetic influence. Correlations with associated general sexual behavior, relationship satisfaction, and attitudes toward sexuality suggest that the self-reported G-spot is to be a secondary pseudo-phenomenon. CONCLUSIONS: To our knowledge, this is the largest study investigating the prevalence of the G-spot and the first one to explore an underlying genetic basis. A possible explanation for the lack of heritability may be that women differ in their ability to detect their own (true) G-spots. However, we postulate that the reason for the lack of genetic variation-in contrast to other anatomical and physiological traits studied-is that there is no physiological or physical basis for the G-spot.

Exploring genetic and environmental influences on miscarriage rates: a twin study.

Abstract Miscarriage is the most common type of pregnancy loss, occurring in up to 15% of clinically recognized pregnancies. Our understanding of the etiology is still limited but is believed to be multifactorial, including endocrine and anatomical abnormalities, immunologic, genetic and lifestyle factors. The aim of this study was to explore whether genetic variability in miscarriage is under any genetic influence. 3234 MZ and DZ female twins completed postal self-completion questionnaires on pregnancies. Rates were adjusted for total number of pregnancies. The relative contribution of genetic and environmental factors to variation in miscarriage was assessed using twin intra-pair correlations and quantified using a variance components model fitting approach. We found 22.7% of our twins reporting having suffered at least one miscarriage. Current age, age at first pregnancy and higher number of pregnancies all had a significant influence on reported miscarriage. The concordance of miscarriage was similar in identical and non-identical twins, 26% and 27%, respectively. Shared environment and predominantly random error and unique environment rather than genetic factors best explained the total variation of miscarriage. To our knowledge, this is the first large twin study exploring heritability of miscarriage which unlike the vast majority of common variable traits, shows no significant genetic influence. In the absence of clear environmental factors, these results suggest the influence of random factors.

Phenotypic and genetic relations between the HEXACO dimensions and trait emotional intelligence.

The present study investigated the location of trait emotional intelligence (trait EI or trait emotional self-efficacy) within the context of the HEXACO model - a more comprehensive personality framework than the conventional Big Five structure. A total of 666 MZ and 526 DZ adult twin pairs from the United Kingdom completed the short form of the Trait Emotional Intelligence Questionnaire (TEIQue-SF) and the short form of the HEXACO Personality Inventory (HEXACO-60). Many significant phenotypic correlations between the TEIQue-SF and the HEXACO-60 were obtained, which were strongest for HEXACO Extraversion, and weakest for HEXACO Honesty-Humility. As was expected, Emotionality was the only HEXACO dimension to correlate negatively with TEIQue-SF scores. Bivariate behavioral genetic analyses revealed that all phenotypic correlations were attributable to common genetic and common nonshared environmental factors. The study confirms the validity of trait EI as a constellation of emotional self-perceptions located at the lower levels of personality.

The genetics and epidemiology of female sexual dysfunction: a review.

INTRODUCTION: Female sexual dysfunction (FSD) is an often underestimated and common problem with serious effects on women's quality of life. Despite a high overall prevalence in the female population--exceeding that of male sexual dysfunction--until recently, little research has focused on this area. In contrast to the successful advances of genetic research in a wide variety of human diseases, genetic exploration in FSD lags far behind. AIM: The aim of this review is to acquaint the reader with the current behavioral and molecular genetic research in the field of FSD. Methods. Because of the heterogeneity of the included studies, we are providing a nonsystematic review. RESULTS: Recent epidemiological and candidate gene studies have suggested a strong genetic influence on female sexual functioning. While these findings provide a clear rationale for more genetic research in the field, they need to be replicated on a much larger scale to be definitive. CONCLUSIONS: Successful identification of biomarkers and novel genes underlying FSD should improve the diagnosis, identification, and treatment of different subgroups. Future pharmacotherapeutic approaches to FSD will benefit from novel targets and the concept that individual variations have a genetic component may help destigmatize our views of sexual problems. Burri AV, Cherkas LM, and Spector TD.

Emotional intelligence and its association with orgasmic frequency in women.

INTRODUCTION: Up to 30% of women suffer from female orgasmic disorder (FOD)-the second most common type of female sexual dysfunction. FOD has been acknowledged to be multifactorial and recent research has implicated the importance of psychosocial risk factors. AIM: The aim of this study is to investigate whether normal variations in emotional intelligence--the ability to identify and manage emotions of one's self and others--are associated with orgasmic frequency during intercourse and masturbation. To our knowledge, this is the first such study in a large unselected population. METHODS: A total of 2035 women from the TwinsUK registry completed questionnaires relating to emotional intelligence and sexual behavior. Global emotional intelligence was measured using the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF). Orgasmic frequency was assessed using two self-constructed questions. MAIN OUTCOME MEASURES: Using Spearman's rank correlation and quartile logistic regression, we investigated whether variations in emotional intelligence are associated with female orgasmic frequency during intercourse and masturbation. RESULTS: Emotional intelligence was not associated with the potential confounders of age and years of education, nor did we find a significant association between emotional intelligence and potential risk factors for FOD such as age, body mass index, physical or sexual abuse, or menopause. We found emotional intelligence to be positively correlated with both frequency of orgasm during intercourse (r = 0.13, P < 0.001) and masturbation (r = 0.23, P < 0.001). Women in the lowest quartile of emotional intelligence had an approximate twofold increased risk of infrequent orgasm (Intercourse = odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4-3.9; Masturbation = [OR] 1.8, [CI] 1.3-2.5). CONCLUSION: Low emotional intelligence seems to be a significant risk factor for low orgasmic frequency. Consideration of this behavioral risk factor may need to be incorporated into research into FOD and possible treatment approaches.

A general factor of personality: evidence from the HEXACO model and a measure of trait emotional intelligence.

The purpose of the present study was to determine if a general factor of personality (GFP) could be extracted from the six dimensions of the HEXACO model and four factors of trait emotional intelligence. Participants were 1,192 pairs of twins (666 MZ pairs, 526 DZ pairs) between the ages of 19 to 86 years, who completed the Trait Emotional Intelligence Questionnaire - Short Form and the HEXACO Personality Inventory - Revised. Principal components analysis yielded a strong GFP accounting for 33% of the variance, on which all variables with the exception of honesty-humility from the HEXACO showed moderate to large loadings. Behavioral genetic (BG) analyses revealed that individual differences in the GFP were entirely attributable to additive genetic and non-shared environmental factors - results that are in accord with previous BG analyses of a GFP. The present study adds to the body of evidence in support of a heritable GFP but an alternative perspective is also discussed.

No clear genetic influences on the association between dyslexia and anxiety in a population-based sample of female twins.

Individuals with dyslexia are at an increased risk for anxiety disorders (e.g. generalized anxiety disorder, stress disorders, panic disorder). The extent to which this association is mediated by genetic and/or environmental influences is unclear. The current study explored the relationship between these two phenotypes using a large population-based twin sample. In total, 940 monozygotic and 903 dizygotic female twin pairs were included in the analyses. The presence of dyslexia and anxiety was determined by self-report of diagnosis by a health professional. Tetrachoric correlations confirmed an association between the two phenotypes, but suggested that there was no evidence for shared genetic risks. Bivariate twin modelling corroborated this finding and indicated the relationship between dyslexia and anxiety is mediated by shared environmental factors. Future research should seek to identifying the environmental factors that increase the vulnerability of individuals with dyslexia to emotional problems should be a priority for future research.

The association between physical activity in leisure time and leukocyte telomere length.

BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.