Etiology of covariation between reading and mathematics performance: a twin study.

The etiology of the observed relationship between reading and mathematics performance was examined by analyzing data from samples of same-sex twin pairs tested in the Colorado Learning Disabilities Research Center. Bivariate phenotypic and genetic structural equation models were fitted to data from 526 twin pairs selected for reading deficits (290 identical and 236 same-sex fraternal) and 355 control pairs (220 identical and 135 same-sex fraternal). Subtests of the Peabody Individual Achievement Test (PIAT; Reading Recognition, Reading Comprehension, and Spelling) were used as measures of reading performance, and scores from the Wechsler Intelligence Scale for Children-Revised (WISC-R) or Wechsler Adult Intelligence Scale-Revised (WAIS-R) Arithmetic subtest, the Wide Range Achievement Test Arithmetic subtest, and the PIAT Math subtest were used as indices for mathematics performance. The results of these confirmatory factor analyses indicate that genetic and environmental covariances between reading and math latent factors do not differ significantly for twin pairs in the proband and control groups. Estimates of heritability for reading performance in the proband and control samples were 0.81 and 0.69, respectively, and those for math performance were 0.88 and 0.67, respectively. Moreover, genetic influences accounted for 83% of the covariation between the reading and math factors in the proband group and for 58% of the covariation between these two latent variables in the control group; in contrast, shared environmental influences did not contribute significantly to the relationship between the reading and math latent factors nor to their independent variation.     

Glucocorticoid receptor binding in twin pairs is affected by shared environment but not by shared genes

We set out to determine whether glucocorticoid receptor activity is affected mainly by genetic or environmental factors. The affinity and capacity of the glucocorticoid receptor was measured using dexamethasone binding in whole leukocytes from 53 monozygotic and 48 dizygotic twin pairs. Receptor binding characteristics assayed from twin pairs on the same day were highly correlated within twin pairs irrespective of zygosity. Apparent Kd was negatively correlated with environmental temperature (R²=0.13, P<0.0001) but this did not confound the intra-pair correlation, suggesting a strong familial component independent of zygosity. Receptor binding parameters were not more closely correlated in monozygotic twins than dizygotic twin pairs indicating that there is no major genetic contribution to receptor binding and that environmental influences predominate. The close similarity in binding between twin pairs in adulthood raises the possibility that familial, non-genetic, factors such as shared early life environment may programme the glucocorticoid receptor.     

Similarities and differences in lipidomics profiles among healthy monozygotic twin pairs

Differences in genetic background and/or environmental exposure among individuals are expected to give rise to differences in measurable characteristics, or phenotypes. Consequently, genetic resemblance and similarities in environment should manifest as similarities in phenotypes. The metabolome reflects many of the system properties, and is therefore an important part of the phenotype. Nevertheless, it has not yet been examined to what extent individuals sharing part of their genome and/or environment indeed have similar metabolomes. Here we present the results of hierarchical clustering of blood plasma lipid profile data obtained by liquid chromatography-mass spectrometry from 23 healthy, 18-year-old twin pairs, of which 21 pairs were monozygotic, and 8 of their siblings. For 13 monozygotic twin pairs, within-pair similarities in relative concentrations of the detected lipids were indeed larger than the similarities with any other study participant. We demonstrate such high coclustering to be unexpected on basis of chance. The similarities between dizygotic twins and between nontwin siblings, as well as between nonfamilial participants, were less pronounced. In a number of twin pairs, within-pair dissimilarity of lipid profiles positively correlated with increased blood plasma concentrations of C-reactive protein in one twin. In conclusion, this study demonstrates that in healthy individuals, the individual genetic background contributes to the blood plasma lipid profile. Furthermore, lipid profiling may prove useful in monitoring health status, for example, in the context of personalized medicine.     

Excess of twins among affected sibling pairs with autism: implications for the etiology of autism

It is widely accepted that genes play a role in the etiology of autism. Evidence for this derives, in part, from twin data. However, despite converging evidence from gene-mapping studies, aspects of the genetic contribution remain obscure. In a sample of families selected because each had exactly two affected sibs, we observed a remarkably high proportion of affected twin pairs, both MZ and DZ. Of 166 affected sib pairs, 30 (12 MZ, 17 DZ, and 1 of unknown zygosity) were twin pairs. Deviation from expected values was statistically significant (P<10(-6) for all twins); in a similarly ascertained sample of individuals with type I diabetes, there was no deviation from expected values. We demonstrate that to ascribe the excess of twins with autism solely to ascertainment bias would require very large ascertainment factors; for example, affected twin pairs would need to be, on average, approximately 10 times more likely to be ascertained than affected non-twin sib pairs (or 7 times more likely if "stoppage" plays a role). Either risk factors (related to twinning or to fetal development) or other factors (genetic or nongenetic) in the parents may contribute to autism.     

Structural analysis of the correlations of genetic markers with physiological indices

The structure of phenotypic and genetic correlations between ABO blood groups, MN, Rh(D), haptoglobins and concentration indications of the total cholesterol, of sugar curve, the levels of systolic and diastolic arterial pressure was studied in twins by the method for cluster analysis (121 monozygotic twin pairs, 120 dizygotic like sex twin pairs and 107 pairs of unlike sex twins). No correlation between the systems analysed and their indications on the phenotypic level was observed. By analysis of genetic correlations, the existence of correlations between the Rh system and arterial pressure, and the total cholesterol concentration, as well as between the ABO system and sugar concentration indexes, was established. Possible genetic causes for correlations obtained are being discussed.     

alpha 2-Adrenergic receptors in platelet membranes of depressed patients: no change in number of 3H-yohimbine affinity

The α₂-adrenergic receptor density in platelet membranes from normal controls and depressed patients was studied using ³H-yohimbine, a potent α₂-adrenergic antagonist, as a radioligand. The KD values of ³H-yohimbine in control and depressed patient samples were 0.92±0.07 nM and 0.97±0.06 nM, respectively. The Bmax values of controls and depressed patients were 240±19 fmoles/mg protein (128±13 receptor platelet, R/PL) and 204±20 fmoles/mg protein (139±14 R/L), respectively. There were no significant differences between the KD and Bmax values of the two groups.     

The bindings of 3H-prazosin and 3H-yohimbine to alpha adrenoceptors in the guinea-pig stomach

Alpha adrenoceptor subtypes have been investigated by radioligand binding study in guinea-pig stomach using 3H-prazosin and 3H-yohimbine. The specific 3H-prazosin binding to guinea-pig stomach was saturable and of high affinity (KD = 1.4 nM) with a Bmax of 33 fmol/mg protein. Specific 3H-yohimbine binding to the tissue was also saturable and of high affinity (KD = 25.5 nM) with a Bmax of 150 fmol/mg protein. Adrenergic drugs competed for 3H-prazosin binding in order of prazosin greater than phentolamine greater than methoxamine greater than norepinephrine greater than clonidine greater than epinephrine greater than yohimbine. These drugs competed for 3H-yohimbine binding in order of yohimbine greater than phentolamine greater than clonidine greater than epinephrine greater than norepinephrine greater than prazosin greater than greater than prazosin greater than methoxamine. We also examined whether dopamine receptors exist in guinea-pig stomach, using radioligand binding study. Specific binding of 3H-spiperone, 3H-apomorphine, 3H-dopamine and 3H-domperidone was not detectable in the stomach. Dopaminergic drugs such as dopamine, haloperidol, domperidone and sulpiride competed for 3H-prazosin binding in order of haloperidol greater than domperidone greater than dopamine greater than sulpiride. Metoclopramide, sulpiride and dopamine competed for 3H-yohimbine binding in order of metoclopramide greater than sulpiride greater than dopamine. These results suggest that guinea-pig stomach has alpha 1 and alpha 2 adrenoceptors and has no specific dopamine receptors. It is also suggested that some dopamine receptor antagonists such as domperidone, haloperidol, sulpiride and metoclopramide have antagonistic actions on alpha adrenoceptors.     

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.     

Heritability of eleven metabolic phenotypes in Danish and Chinese twins: A cross‐population comparison

Objectives : A twin‐based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods : Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18‐67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18‐69). Twin modeling was performed on full and nested models with the best fitting models selected. Results : Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. Conclusions : Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.     

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 color and structure of the human iris. 2. Studies of 200 twins]

Subject of the present report is an investigation of the heredity of 30 iris characteristics. The material basis of this sample of twins (100 monozygotic and 100 dizygotic pairs), the largest ever taken as a basis for the purpose of iris research, consists of standardized colour photographs of the examined persons' irises and iris-microscopic observations. The pairs of twins are compared to 100 non-related casual pairs in order to render a better estimation of the degree of heredity of the features possible. On every occasion several classes were constituted for the concordance verification. These classes result from the number of the classes of the forms of markedness and present different levels of similarity. The different distribution of the twin pairs and the control pairs on the concordance classes are always examined for their statistical significance, and for each group of pairs a concordance value is computed. The intervals between the concordance values of the monozygotic and dizygotic pairs and the control pairs indicate the degree of heredity of the investigated feature. Taking all the compiled factors and conditions into consideration, an evaluation of the features as heredity features is made. Though a hereditary component can be observed for all iris characteristics, only about a third could be called heredity features. Quantity of pigment and the hitherto undescribed limiting layer folds were evaluated as "very good", whereas pigment colour in the fine analysis, quality of the anterior stroma leaf, frequency of iris crypts and iris frill position were judged as "good". Tone of blue, markedness of Woelfflin nodules, quantity and markedness of contractional rings could be evaluated as "moderately good" as to their heredity. On the basis of the prior concordance investigations for each of the 300 pairs, a "similarity index" and a "concordance index" were computed in order to arrive at evidence as to the degree of similarity of the single pairs; i.e. in order to detect the limits of the similarity between non-identical twins and the dissimilarity between identical twins. This concluding investigations lead to the question of the possibility of a diagnosis of genetic identicalness solely on the basis of the comparison of irises.     

Monthly trend and seasonal variation in twinning rate in Japan, 1975–1994

We examined birth records from Japanese statistics, 1975–1994, to investigate the seasonality of twin births. We could identify 198 924 pairs of twins (97.9% of all the registered twin records) and estimated the numbers of mono- and dizygotic twin pairs. The seasonal index of the twinning rate for each month was calculated by dividing the crude rate by the estimated trend value for the month. There were significant variations in the seasonal index for overall, dizygotic and monozygotic twinning rates. Peak months with values more than 3% higher than expected were July and October–December for dizygotic twins, and April and June for monozygotic twins; these seasonalities were statistically significant by analysis of variance and the patterns were similar in recent years, with a sharp increase in the total twinning rate. When observed year-by-year, however, there were years that did not show these typical seasonalities. It is suggested that the mechanisms for probable seasonal variations in twinning rates are different for dizygotic and monozygotic twin pregnancies, and that factors involved in these variations are not effective every year. Received: 2 September 1998 / Revised: 6 May 1999 / Accepted: 26 May 1999     

Growth patterns in young adult monozygotic twin pairs discordant and concordant for obesity.

Weight discordance is very rare in monozygotic (MZ) twin pairs; when found, however, such pairs are advantageous in the search for either environmental or epigenetic causes and consequences of obesity. We analyzed the growth patterns of young adult MZ pairs discordant and concordant for obesity. Screening 5 consecutive birth cohorts (1975-1979) of 22- to 27-year-old Finnish twins (the FinnTwin16 study), we found 14 obesity discordant (Body Mass Index [BMI] difference > or = 4 kg/m2) MZ pairs out of 658. Ten pairs participated in clinical studies. Nine concordant pairs (BMI difference < or = 2 kg/m2) were examined as controls. Lifetime measured heights and weights recorded in hospitals and health centers were traced manually. Height development was similar in all the co-twins of both groups. The weight differences between the co-twins of the discordant pairs began to emerge at 18 years leading to an average discordance of 16.4 kg, 5.6 kg/m2 (p for both = .005) at 25.7 years. The heavier co-twin weighed 221 g (p = .066), 1.0 kg/m2 (p = .01) more already at birth than the leaner, but the differences waned by 6 months of age and reappeared only after adolescence. Both the leaner and the heavier co-twins of the discordant pairs weighed more than expected by the singleton reference values (Cole et al., 1998) after 8 years. The concordant co-twins, on the other hand, grew similarly and after 6 months, their mean growth was not distinguishable from the singleton patterns. Young adulthood represents a critical period of gaining weight irrespective of genetic background in this twin sample.     

Resiliency factors protecting against teenage alcohol use and smoking: influences of religion, religious involvement and values, and ethnicity in the Missouri Adolescent Female Twin Study.

The objective of this study was to investigate the contribution of ethnicity (African American vs European/other ancestry), family religious affiliation, religious involvement, and religious values, to risk of alcohol and cigarette use in adolescent girls; and to estimate genetic and shared environmental effects on religious involvement and values. Telephone interviews were conducted with a sample of female like-sex twin pairs, aged 13-20 (n = 1687 pairs, including 220 minority pairs), as well as with one or both parents of twins aged 11-20 (n = 2111 families). These data, together with one-year follow-up twin questionnaire data, and two-year follow-up parent interview data, were used to compare ethnic differences. Proportional hazards regression models and genetic variance component models were fitted to the data. Despite higher levels of exposure to family, school and neighborhood environmental adversities, African American adolescents were less likely to become teenage drinkers or smokers. They showed greater religious involvement (frequency of attendance at religious services) and stronger religious values (eg belief in relying upon their religious beliefs to guide day-to-day living). Controlling for religious affiliation, involvement and values removed the ethnic difference in alcohol use, but had no effect on the difference in rates of smoking. Religious involvement and values exhibited high heritability in African Americans, but only modest heritability in EOAs. The strong protective effect of adolescent religious involvement and values, and its contribution to lower rates of African American alcohol use, was confirmed. We speculate about the possible association between high heritability of African American religious behavior and an accelerated maturation of religious values during adolescence.     

Connexin 26 35delG does not represent a mutational hotspot

Recent evidence suggests that the susceptibility to respiratory distress syndrome (RDS) is partly explained by genetic variation in the surfactant proteins (SP) SP-A and SP-B. The present study was designed to evaluate the concordance difference method and candidate gene analysis, in parallel, for the investigation of genetic susceptibility to RDS. We studied 100 same-sex twin pairs with established RDS in at least one twin. The difference in RDS concordance rates between the monozygotic (MZ) and dizygotic (DZ) twin pairs as evidence of a genetic influence was evaluated, and the SP-A and SP-B genes were investigated for potential associations with the susceptibility to RDS. The concordance rates of RDS were 54 and 44% in the MZ and DZ pairs, respectively. The concordance difference of 10% was not significant [95% confidence interval (CI) -0.1 to +0.3, P=0.32], suggesting a low hereditary impact. However, the SP-B Ile131Thr polymorphism was associated with RDS. The threonine allele was associated with an increased risk of RDS [odds ratio (OR) 2.2, 95% CI 1.4-3.5, P=0.0014]. This was particularly apparent in first-born male infants (OR 6.2, 95% CI 2.4-16.3, P<0.001). The degree of prematurity (<32 weeks OR 2.0, 95% CI 1.1-3.7, P=0.021) and birth order (second-born OR 3.1, 95% CI 1.3-7.4, P=0.009) were the clinical variables affecting the risk of RDS. An association between the SP-B Ile131Thr polymorphism and RDS was found. The threonine allele was associated with the risk of RDS, particularly in the first-born twin infants. The concordance difference between MZ and DZ twin pairs underestimates the genetic impact on the risk of RDS. The traditional twin concordance study is insufficient to evaluate genetic predisposition to RDS or other diseases that are confounded by the birth order or multiple pregnancy in itself.     

Genetic and environmental influences on the relationship between aggression and hyperactivity-impulsivity as rated by teachers and parents.

This study examined genetic and environmental contributions to the covariance between aggression and hyperactivity-impulsivity as rated by twins' teachers and parents. Sex-differences in these genetic and environmental contributions and rater bias/sibling interaction effects were of interest as well. Part of an ongoing nation-wide twin-family study of behavioral development and health habits, the sample consisted of 1636 Finnish twin pairs ascertained from five consecutive and complete twin birth cohorts. Data were collected at ages 11-12, using teacher and parental rating forms of the Multidimensional Peer Nomination Inventory. Bivariate analyses were performed using structural equation modeling allowing sex-limitation effects. Results show that, in addition to significant genetic and environmental influences specific to each behavior, aggression and hyperactivity-impulsivity share common genetic and environmental etiology. Results provide evidence that both genetic and environmental factors are important in creating the observed correlation between aggression and hyperactivity-impulsivity.     

Bias of heritability estimates from twin data in presence of errors of zygosity determination

Simple heritability estimators of continuous as well as discrete traits from twin data are known to overestimate the degree of genetic determination of the measured traits for several reasons. Errors of zygosity determination will, however, underestimate the true heritability. The bias due to wrong assignment of dizygous twin pairs into monozygous type is evaluated here, and the results indicate that this negative bias has a compensatory effect on the estimate of the degree of genetic determination when other factors of similarity between twin pairs are taken into account. It is shown that when an estimate of zygosity error is available, the bias due to this factor can be evaluated quantitatively, and hence the adjustment for zygosity error can be incorporated in the estimation of the degree of genetic determination of a trait. Although this theory is explicitly developed here for twin studies, the general principle also applies for other types of errors of determining the degree of biological relationships for estimation of heritability, in which case this type of error may be more important than the simple zygosity error.