Pairs of Genetically Unrelated Look-Alikes

Relationships of physical resemblance to personality similarity and social affiliation have generated considerable discussion among behavioral science researchers. A “twin-like” experimental design (involving genetically unrelated look-alikes, U-LAs) explores associations among resemblance in appearance, the Big Five personality traits, self-esteem, and social attraction within an evolutionary framework. The Personality for Professionals Inventory (PfPI), NEO/NEO-FFI-3, Rosenberg Self-Esteem Scale, and a Social Relationship Survey were variously completed by 45 U-LA pairs, identified from the “I’m Not a Look-Alike” project, Mentorn Media, and personal referrals. The mean U-LA intraclass correlations were negligible for all Big Five personality traits on the PfPI and NEO/NEO-FFI-3 (r_i =??.02 and???.04, respectively). In contrast, mean r_i values of .53 and .15 for monozygotic (MZA) and dizygotic (DZA) reared-apart twins, respectively, have been reported for these personality measures. The U-LA self-esteem correlation (r_i =??.18) was also below the correlations reported for MZ and DZ reared-together twins (r_{i =} .31 and .13, respectively). Finally, far fewer U-LAs expressed close social relationships (20%) than MZA (80%) and DZA (65%) twins. The present study extends earlier findings indicating that appearance is not meaningfully related to personality similarity and social relatedness. The criticism that MZ twins are alike in personality because their matched looks invite similar treatment by others is refuted. A more judicious interpretation is reactive genotype-environment correlation, namely that MZ twins’ similar personalities evoke similar reactions from others. MZ twins’ close social relations most likely derive from their perceptions of genetically based within-pair similarities that are lacking in U-LAs.     

Monozygotic VS. Dizygotic Twin Behavior in Artificial Mouse Twins

Adult inbred mice of an isogenic strain (AKR/NHan or C57BL/6J Han) differ in social (sexual and agonistic), emotional and psychomotoric behavior, depending on the kind of manipulation to which they were subjected at an early ontogenetic stage. Monozygotic twins (MZT) from eight-cell stages halved and transferred to uterine foster mothers were compared with dizygotic twins (DZT) from nonreduced but transferred eight-cell stages and with naturally born animals (NBA). Generally, early embryonic conditions predict the behavioral characteristics of the adult animals to a high degree. The MZT are motorially less active, less emotional, less aggressive and less socially interested than DZT and NBA. In tests of spontaneous social behavior (allogrooming, anogenital licking, mounting, fighting), as well as in tests for emotionality (open field: crossed fields and defecation), these behavioral patterns occurred less frequently in MZT than in DZT; the NBA were mostly intermediate. The copulatory pattern of male MZT differs from that of male DZT by a shortage of intromission latency and duration; furthermore, MZT pairs do not build up a steady rank order in competitive copulation tests, as opposed to DZT and NBA pairs. In a test for psychomotoric behavior (swimming), the MZT prefer "floating" as a survival strategy, wheras the DZT and NBA prefer "adult swimming." Therefore, it can be concluded that these behavioral differences may be caused by the particular psychosocial environment in which the twins grow up or may be due to early prenatal peculiarities, such as inadequate synchronization of the developmental status of uterus and embryo.     

The mechanism of emergenesis

Since each individual produced by the sexual process contains a unique set of genes, very exceptional combinations of genes are unlikely to appear twice even within the same family. E. O. Wilson (1978)The intraclass correlations of monozygotic twins who were separated in infancy and reared apart (MZA twins) provide estimates of trait heritability, and the Minnesota Study of Twins Reared Apart [MISTRA: Bouchard et al. (1990), The sources of human psychological differences: the Minnesota study of twins reared apart, Science 250, 223-228] has demonstrated that MZA pairs are as similar in most respects as MZ pairs reared together. Some polygenic traits--e.g. stature, IQ, harm avoidance, negative emotionality, interest in sports--are polygenic-additive, so pairs of relatives resemble one another on the given trait in proportion to their genetic similarity. But the existence and the intensity of other important psychological traits seem to be emergent properties of gene configurations (or configurations of independent and partially genetic traits) that interact multiplicatively rather than additively. Monozygotic (MZ) twins may be strongly correlated on such emergenic traits, while the similarity of dizygotic (DZ) twins, sibs or parent-offspring pairs may be much less than half that of MZ pairs. Some emergenic traits, although strongly genetic, do not appear to run in families. MISTRA has provided at least two examples of traits for which MZA twins are strongly correlated, and DZA pairs correlate near zero, while DZ pairs reared together (DZTs) are about half as similar as MZTs. These findings suggest that even more traits may be emergenic than those already identified. Studies of adoptees reared together (who are perhaps more common than twins reared apart) may help to identify traits that are emergenic, but that also are influenced by a common rearing environment.     

Intrinsic and extrinsic religiousness: genetic and environmental influences and personality correlates.

This report presents findings for the Intrinsic (IR) and Extrinsic (ER) religiousness scales from the Minnesota Study of Twins Reared Apart. The scales were shown to be internally consistent, sufficiently distinct from the scales of the California Psychological Inventory and the Multidimensional Personality Questionnaire and unrelated to a number of measures of response style to justify treating them as distinct traits. The I scales also showed considerable evidence of construct validity in its correlations with religious fundamentalism and authoritarianism as assessed by the MMPI and Altemeyer's Right-Wing Authoritarianism scale. Data on IR and ER from 35 pairs of monozygotic twins reared apart (MZA) and 37 pairs of dizygotic twins reared apart (DZA) were fitted to a biometric model and demonstrated significant heritability (0.43 and 0.39), with a model containing genetic plus environmental factors fitting significantly better than a model containing only an environmental component. Twin similarity could not be explained by placement on a self-reported measure of family Moral Religious Emphasis as measured by the Family Environment Scale.     

Genetic basis of human female pelvic morphology: a twin study

To examine the relative role of genetic and environmental factors on pelvic morphology, data on 60 pairs of female twins (30 monozygotic (MZ) and 30 dizygotic (DZ)) were analyzed. Fourteen pelvic measurements were normally distributed, and two were not. Association of twin type with the mean value of a trait was found in only 1 out of 8 traits. Heterogeneity of variance between zygosities was observed in 4 pelvic traits (50%), invalidating within-pair estimates of genetic variance for these traits. Evidence of stronger environmental covariance for MZ than DZ twins was observed for only one trait (sitting height iliocristale). A significant genetic component of variation was observed for age at menarche and in the pelvic area. In instances where inequality of variances between zygosities was demonstrated, total among-pair and within-pair mean squares were larger for dizygotic than for monozygotic twins. This is interpreted as evidence of greater environmental influence between zygosities. Environmental modification was not of the same magnitude in various pelvic traits. Bitrochanteric breadth had the highest magnitude of cultural heritability, indicating that cultural factors played an important role in determining hip breadth.     

Genetic and environmental effects on age at menarche,and its relationship with reproductive health in twins

INTRODUCTION:

Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors.

OBJECTIVE:

Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche.

METHODOLOGY:

A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers’ formula and maximum likelihood.

RESULTS:

Heritability was found to be 66% using Falconers’ formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%).

DISCUSSION:

Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins.

CONCLUSION:

It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.     

Age at menarche as a fitness trait: nonadditive genetic variance detected in a large twin sample.

The etiological role of genotype and environment in recalled age at menarche was examined using an unselected sample of 1,177 MZ and 711 DZ twin pairs aged 18 years and older. The correlation for onset of menarche between MZ twins was .65 +/- .03, and that for DZ pairs was .18 +/- .04, although these differed somewhat between four birth cohorts. Environmental factors were more important in the older cohorts (perhaps because of less reliable recall). Total genotypic variance (additive plus nonadditive) ranged from 61% in the oldest cohort to 68% in the youngest cohort. In the oldest birth cohort (born before 1939), there was evidence of greater influence of environmental factors on age at menarche in the second-born twin, although there was no other evidence in the data that birth trauma affected timing. The greater part of the genetic variance was nonadditive (dominance or epistasis), and this is typical of a fitness trait. It appears that genetic nonadditivity is in the decreasing direction, and this is consistent with selection for early menarche during human evolution. Breakdown of inbreeding depression as a possible explanation for the secular decline in age at menarche is discussed.     

Genetic effects in human skeletal muscle fiber type distribution and enzyme activities

The purpose of the study was to estimate the genetic effect for skeletal muscle characteristics using pairs of nontwin brothers (n = 32), dizygotic (DZ) twins (n = 26), and monozygotic (MZ) twins (n = 35). They were submitted to a needle biopsy of the vastus lateralis for the determination of fiber type distribution (I, IIa, IIb) and the following enzymes were assayed for maximal activity: creatine kinase, hexokinase, phosphofructokinase (PFK), lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase (OGDH). For the percentage of type I fibers, intraclass correlations were 0.33 (p less than 0.05), 0.52 (p less than 0.01), and 0.55 (p less than 0.01) in brothers and DZ and MZ twins, respectively. MZ twins exhibited significant within-pair resemblance for all enzyme activities (0.30 less than or equal to r less than or equal to 0.68). In spite of these correlations, genetic analyses performed with the twin data alone indicated that there was no significant genetic effect for muscle fiber type I, IIa, and IIb distribution and fiber areas. Although there were significant correlations in MZ twins for all muscle enzyme activities, the often nonsignificant intraclass coefficients found in brothers and DZ twins suggest that variations in enzyme activities are highly related to common environmental conditions and nongenetic factors. However, genetic factors appear to be involved in the variation of regulatory enzymes of the glycolytic (PFK) and citric acid cycle (OGDH) pathways and in the variation of the oxidative to glycolytic activity ratio (PFK/OGDH ratio). Data show that these genetic effects reach only about 25-50% of the total phenotypic variation when data are adjusted for age and sex differences.     

Within-pair testosterone covariation and reproductive output in Greylag Geese Anser anser

In monogamous animals, reproductive success may vary considerably among pairs. To study this variation, we focussed on reproductive events and the circannual hormonal co-ordination within pairs during the reproductive cycle. Testosterone was chosen as covariable for both sexes because of its mediator function between behaviour and physiology. In a flock of free-living Greylag Geese Anser anser , individual faecal samples were collected weekly from 23 pairs over a complete annual cycle. From the faeces, equivalents of testosterone, oestrogen and other steroid hormones were analysed by enzyme immunoassay. In contrast to correlations between male and female testosterone, no correlations were found between oestrogen-oestrogen or oestrogen-testosterone. Therefore, only testosterone (T) is considered here. Sex-specific differences in T were in amplitude rather than in the annual timing of maxima and minima. However, the annual timing varied to some degree between individuals within sexes. Therefore, we examined the degree of annual testosterone correlation (TC) within pairs. Pairs that nested had significantly higher TC over the year than pairs that did not. The higher the within-pair TC, the larger the clutches and the heavier the eggs. Also, TC in the year investigated was positively and significantly correlated with the pairs' long-term reproductive output. No correlation was found between TC and the duration of the pair-bond, individual age, or age difference from pair partner. We suggest that TC is a measure of behavioural synchrony and, therefore, pair-bond quality. We consider whether within-pair TC results from mate choice.     

Effects of chorion type on variation in cord blood cholesterol of monozygotic twins.

Cholesterol levels were measured in the cord blood of 30 pairs of monochorionic and 22 pairs of dichorionic monozygotic (MZ) twins. Cholesterol levels were found to be significantly higher in female twins when data was combined over chorion type. The type of chorionic development had no significant effect on variation among twin pairs. Chorion type did, however, have a significant effect on the within-pair variation. The variation within dichorionic pairs was more than five times that within monochorionic pairs (P less than .01). This result suggests that the variation in placentation has a significant effect on within-pair variation in serum cholesterol of newborn MZ twins.     

Contribution of genetic and environmental factors to variation in body compartments--a twin study in adults

This study aimed at analyzing the contribution of genetic and environmental factors on phenotypic variation of various traits of body composition. Subjects were 30 same-sexed pairs of twins including 20 monozygous (MZ) and 10 dizygous (DZ) pairs, aged 19-62 years. Zygosity was determined by DNA typing and morphological diagnosis. Body composition parameters (fat mass FM, lean body mass LBM, body cell mass BCM, extracellular mass ECM, total body water TBW, extracellular water ECW, and intracellular water ICW) were estimated by tetrapolar bioelectrical impedance analysis. Potential environmental factors influencing body composition (number of children, sporting activity and smoking behaviour) were determined by questionnaires. Heritabilities for traits of body composition were calculated by use of the twin method. Intraclass correlation is > 0.80 for the variation of LBM, BCM, ECM, TBW, ECW, and ICW in both MZ and DZ twins. Estimated heritability (h2) for FM, LBM, BCM, ECW, TBW, ECW, and ICW is 65%, 77%, 79%, 83%, 76%, 68%, and 82%, respectively. The h2 values for FM and LBM are consistent with those reported in other twin studies. For BCM, ECM, ECW and ICW, no comparative h2 estimates exist. Within-pair differences in body compartments do not change with increasing age in MZ and DZ twin pairs (p > 0.05). Stepwise multiple regression analyses indicate that zygosity, age, sex, number of children, sporting level and smoking behaviour do not significantly predict within-pair differences for weight, BMI, FM, LBM, TBW, ECW and ICW (each, p > 0.05). In contrast, sex and the number of children explain together 27% of observed within-pair differences for BCM. Zygosity is the only significant predictor of within-pair differences for ECM and height, explaining 20% (p = 0.008) and 36% of variance, respectively (p < 0.0001). Results indicate that genetic factors exert stronger influences on body composition than the considered environmental traits.     

Relationship of fat mass and serum estradiol with lower extremity bone in persons with chronic spinal cord injury

In the spinal cord injury (SCI) population, a relationship between adiposity and leg bone has not been reported, nor one between serum estradiol and leg bone mass. A cross-sectional, comparative study of 10 male pairs of monozygotic twins discordant for SCI was performed. Relationships were determined among bone mineral density (BMD), bone mineral content (BMC), lean mass, fat mass, and serum sex steroids. In the twins with SCI, significant relationships were evident between leg BMD or BMC with total body percent fat (r2= 0.49, P < 0.05; r2= 0.45, P = 0.05), leg fat mass (r2 = 0.76, P < 0.0005; r2= 0.69, P = 0.005), and serum estradiol (r2= 0.40, P = 0.05; r2= 0.37, P = 0.05). By stepwise regression analysis, in the twins with SCI, leg fat mass was found to be the single most significant predictor of leg BMD or BMC (F = 12.01, r2= 0.76, P = 0.008; F = 50.87, r2= 0.86, P < 0.0001). In the able-bodied twins, leg lean mass correlated with leg BMD and BMC (r2= 0.58, P = 0.01; r2= 0.87, P = 0.0001). By use of within-pair differences, significant correlations were found for leg lean mass loss with leg BMD loss (r2= 0.56, P = 0.01) or leg BMC loss (r2= 0.64, P = 0.0005). In conclusion, in twins with SCI, significant correlations were observed between fat mass and leg BMD or BMC as well as between serum estradiol values and leg BMD. The magnitude of the leg muscle mass loss was correlated with the magnitude of bone loss.     

Blood glutathione and cysteine concentrations in twin children

Glutathione and cysteine are major antioxidants in blood that are associated with health and longevity. To ensure their measurement, careful attention to avoid auto-oxidation is necessary to stabilize the samples. Since no report of these compounds has been reported in children, our goal was to determine their levels of reduced and oxidized glutathione (GSH and GSSG) and cysteine (Cys and CSSC), To this end, 140 healthy children, ages 2 to 9 years from the Louisville Twin Study were studied. Blood samples were collected and analyzed for GSH, GSSG, Cys, and CSSC by our HPLC dual electrochemical method. The results showed that GSH and total GSH (GSH + GSSG) levels for monozygotic (MZ) twins were significantly higher (P < 0.001) than levels for dizygotic (DZ) twins. However, the opposite occurred for Cys and total Cys (Cys + CSSC) in that the levels were significantly higher for DZ twins than for MZ twins. (P < 0.005-0.013). In spite of this marked difference in zygosity, the within-pair correlations for twin pairs used for estimating heritability suggested that there was a major environmental influence for total GSH and total Cys. Finally. GSH levels were significantly lower for young (2-9 years) children than adults (P < 0.001).     

The effects of chorion type on variation in IQ in the NCPP twin population.

The 7-year IQ scores (WISC) of 116 white and 143 black nonmalformed twins of known zygosity and placental type were ascertained from the NINCDS Collaborative Perinatal Project (NCPP). The type of chorion and zygosity had no significant effect on the mean IQ or among-pair variation. In white monozygotic twins, however, analysis of variance revealed a significantly greater within-pair mean square for dichorionic twins than monochorionic twins. On the other hand, the white dichorionic monozygotic (MZ) and dizygotic (DZ) within-pair mean squares were quite similar. These findings were not evident in blacks for either of the within-pair comparisons. In addition, estimates of genetic variance were dependent upon MZ chorion type in both races. These data suggest to us that (1) in white twin pairs dichorionic placentas are of greater influence than the similarity or dissimilarity of genomes with regard to intrapair IQ development, and (2) failure to consider chorion type may introduce a serious bias in the interpretation of genetic variance estimates of IQ variability.     

Size at birth, fasting glucose and insulin levels and insulin resistance in adult twins.

Studies in singletons have found an association between birthweight and Type 2 diabetes in adult life. The aim of this study was to investigate whether this association could also be seen in twins. 59 monozygotic (MZ) and 69 dizygotic (DZ) same-sex twin pairs aged 19-50 years and 89 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from a local obstetric database. Associations between adult glucose, HbA(1)C and insulin levels and insulin resistance and birthweight were assessed by linear regression with adjustment for confounding variables. Twins were significantly lighter at birth than singleton controls, but there were no significant differences in adult weight, glucose, HbA(1)C and insulin levels or insulin resistance between twins and controls. The relationship between birthweight and fasting glucose and insulin levels, and insulin resistance was not significantly different from zero in either twins or controls, but birthweight was significantly negatively associated with HbA(1)C only in controls. There was no evidence of a difference between MZ and DZ twins in unpaired or within-pair analysis. These results provide little evidence that low birthweight in twins increases the risk of impaired glucose-insulin metabolism in young adults or that genetic factors can account for the association observed in singletons.     

Effects of twinning, birth size, and postnatal growth on glucose tolerance and hypothalamic-pituitary-adrenal function in postpubertal sheep

Low birth weight is associated with postnatal physiological changes, including impaired glucose tolerance and increased cortisol secretion, that may predispose to disease in adulthood. Twins are born lighter than singletons, but there are conflicting data regarding the association between birth weight and postnatal physiology in twins. We studied glucose tolerance and ACTH and cortisol responses to a combined corticotropin-releasing hormone and arginine vasopressin (CRH + AVP) challenge in postpubertal female twin (n = 7 twin pairs) and singleton (n = 13) sheep from the same flock. There were no differences in glucose tolerance between twins and singletons and no association with birth weight. Twins had a greater ACTH (P < 0.05), but not cortisol, response to CRH + AVP than singletons. ACTH area under the curve was inversely related to birth weight in both singletons [R(2) = 0.31, P = 0.05; -8,311 (SD 3,736) pg.min.ml(-1).kg(-1)] and twins (R(2) = 0.49); in twins, this was due to the within-twin pair rather than the between-twin pair coefficient in the regression analysis [P = 0.02, -26,856 (9,806) vs. P = 0.1, 8,619 (4,950) pg.min.ml(-1).kg(-1)]. We conclude that the reduced fetal growth in twins has postnatal consequences for hypothalamic-pituitary-adrenal function and that this is determined by factors specific to the fetus (within-twin pair) rather than by shared maternal factors (between-twin pair). Studies investigating the associations between fetal growth and postnatal outcomes in twins benefit from an appropriate singleton control group and from analyses evaluating the contribution from both between- and within-pair coefficients in twins.     

Single versus serial assessment of skeletal age: Either,both or neither?

Assessments of skeletal age are a valuable adjunct to the clinical evaluation of physical maturity but are more meaningful when considered in relation to chronological age, especially over time, than as separate entities. Data on 51 girls from the Child Research Council study series gave a correlation coefficient of 0.51 between skeletal age (SA) at menarche and chronological age (CA) at menarche — a value in close agreement with data reported from other studies. With a range in SA of 11.58 to 14.89 years, these data were examined further for changes in SA related to timing of adolescence. SA was greater than CA in each of the nine girls whose menarche occurred between 10.5 and 12 years of age. SA was equal to CA in one girl, greater than CA in eight girls and less than CA in 11 girls with menarche between 12.15 and 13.4 years. Of the 22 girls with menarche after 13.5 years, one had SA = CA at 14.89 years and the other 21 all had SA less than CA. An r of 0.84 was calculated between the values of CA minus SA at menarche and CA at menarche. Similar relationships were found between SA and CA at age of maximum increment in growth in height for these girls and for 53 boys in the study series. Longitudinal data for height, weight and SA for four boys and five girls demonstrate the problems of prediction of the timing of adolescence and of adult size from skeletal ages in the childhood years.     

Using bivariate models to understand between- and within-cluster regression coefficients, with application to twin data

In the regression analysis of clustered data it is important to allow for the possibility of distinct between- and within-cluster exposure effects on the outcome measure, represented, respectively, by regression coefficients for the cluster mean and the deviation of the individual-level exposure value from this mean. In twin data, the within-pair regression effect represents association conditional on exposures shared within pairs, including any common genetic or environmental influences on the outcome measure. It has therefore been proposed that a comparison of the within-pair regression effects between monozygous (MZ) and dizygous (DZ) twins can be used to examine whether the association between exposure and outcome has a genetic origin. We address this issue by proposing a bivariate model for exposure and outcome measurements in twin-pair data. The between- and within-pair regression coefficients are shown to be weighted averages of ratios of the exposure and outcome variances and covariances, from which it is straightforward to determine the conditions under which the within-pair regression effect in MZ pairs will be different from that in DZ pairs. In particular, we show that a correlation structure in twin pairs for exposure and outcome that appears to be due to genetic factors will not necessarily be reflected in distinct MZ and DZ values for the within-pair regression coefficients. We illustrate these results in a study of female twin pairs from Australia and North America relating mammographic breast density to weight and body mass index.     

The variation in age at menarche: an indicator of historic developmental tempo

Ample literature describes the history of the association between the advances in the health and wealth of people, and mortality rates, life expectancy and adult height. Twenty-nine German studies with n > 200 subjects published since 1848 on menarcheal age, were reanalyzed, and 101 studies from various other European and non-European countries. On average, mean age at menarche declined since the mid-19th century. Historic urban samples tended to decline earlier than rural groups, upper class women earlier than working class women. In Germany, minimum values for the age at menarche were seen already between the two World Wars (Leipzig 12.6 years in 1934, Halle 13.3 years in 1939). Values for mean age and SD for age at menarche were strongly associated. With improving historic circumstances, the two parameters declined in parallel. The standard deviation for menarcheal age dropped from over 2.5 years in mid-19" century France to little more or even less than 1 year in most modern countries. In the German studies the correlation between menarcheal age and SD was almost complete with r = 0.96 (y = 0.35x - 3.53). Similar associations between mean age at menarche and SD for age were found in other European countries. The obvious and immediate effects of historic events on menarcheal age, and particularly on the age distribution, indicate that menarche is a sensitive indicator of public health and wealth, and may be an appropriate estimator for the socio-economic background of historic populations.     

Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain.

OBJECTIVES--To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. DESIGN--Cross sectional twin study. SETTING--Twin population based in Britain. SUBJECTS--95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. MAIN OUTCOME MEASURES--Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. RESULTS--At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. CONCLUSIONS--The findings that in postmenopausal women in Britain bone density-particularly at the hip and spine-is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis.