Predicting zygosity in Norwegian twin pairs born 1915–1960

Present addresses of 12,752 like-sexed twin pairs born in the period 1915-1960 were identified. A questionnaire, concerning the similarity of pair members, was sent to all individuals. Responses were obtained from 83.7% of the subjects. The zygosity of 207 pairs was established by examination of genetic markers. By using discriminant analysis on the responses from this subgroup, functions were obtained for prediction of zygosity from questionnaire data. It was estimated that 2.4% of the pairs would be misclassified if the questionnaire responses from both pair members were used, and 3.9% if only the response from one of the twins was used. Accordingly, zygosity could be predicted with satisfactory reliability also for twin pairs where only one of the twins had responded. The predicted percentage of monozygotic (MZ) pairs among pairs where one or both twins had responded, was 39.4 (4,402/11,175). The percentage of MZ pairs was significantly lower (34.5) in death-discordant pairs than in pairs in which both twins were alive (39.6). The zygosity questionnaire data are sufficient to adequately score twin pairs for zygosity in the great majority of cases.     

Twin study of genetic and aging effects on X chromosome inactivation

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18-53 years), 82 elderly MZ twin pairs (55-94 years), 146 young dizygotic (DZ) twin pairs (20-54 years) and 112 elderly DZ twin pairs (64-95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001). Our data suggest that the increase in skewing occurs after age 50-60 years. The intraclass correlation was 0.61 and 0.58 in young and elderly MZ twin pairs, and 0.08 and 0.09 in young and elderly DZ twin pairs. Biometric analysis showed that dominant genetic effects accounted for 63 and 58% of the variance of XIP in the young and elderly twin pairs, respectively. The dominant genetic effect and the shared environment for monochorionic MZ twins may explain the high intraclass correlation for the MZ twin pairs compared to the DZ twin pairs. We did not observe a significant decrease in the intraclass correlation in elderly MZ twins compared to young MZ twins, which would be expected if age-related skewing were due to stochastic factors. We conclude that the increased skewing with age implies that a genetically dependent selection of blood cells take place.     

Iron metabolism in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome

Fetal iron metabolism was investigated in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples were obtained both in utero and at birth from MC twins with TTTS (n = 23) and without TTTS (n = 18). In a second group of 30 twin pairs (15 with and 15 without TTTS), liver iron content was assessed by using archived paraffin wax-embedded blocks. Serum ferritin was determined by radioimmunoassay and values are given as gestation independent Z-scores and expressed as mean with 95% confidence intervals. Ferritin concentrations in the recipients were higher than in the donors both in utero (P < 0.01) and at birth (P < 0.01). Fetal serum ferritin in non-TTTS twins were similar to the recipient twins but higher than the donor twins (P < 0.05). A significant association was found between ferritin concentrations, the total red blood cell count and haemoglobin in the TTTS twin pairs (P < 0.01) and the non-TTTS twins as a group (P < 0.01). The total stainable liver iron was comparable between twin pairs in the TTTS and non-TTTS groups. This study fails to provide evidence of iron overload in the recipient and depletion in the donor twins and, thereby, questions the validity of the conventional theory of inter-twin transfusion as the cause of TTTS.     

Chromosome findings in twins with early-onset autistic disorder

In a twin study of autistic disorder, chromosome analyses were carried out in nine pairs of monozygotic (MZ) twins, two pairs of dizygotic (DZ) twins, one set of MZ triplets, one single twin from a MZ pair, and seven single twins from DZ pairs. All but one of the MZ sets were concordant for autistic disorder; all DZ pairs were discordant. Fragile X(q)(27.3) was found in one pair of MZ twins and in MZ triplets, i.e., in 9% of the population with autistic disorder. A marker chromosome of unknown origin was detected in a male twin with autistic disorder from a discordant DZ pair.     

Heritability of Parkinson disease in Swedish twins: a longitudinal study

Previous twin studies report no heritability of Parkinson's disease (PD) based on cross sectional information. Here, we apply a longitudinal design and re-evaluate cross sectional data in the population-based Swedish Twin Registry (STR) using clinical as well as hospital discharge and cause of death diagnoses. In the longitudinal analyses (based on 46,436 individuals), we identified 542 twins with PD and 65 twins with Parkinsonism. Concordance rates for PD were 11% for monozygotic and 4% for same-sexed dizygotic twin pairs, with a heritability estimate of 34%. Concordance rates for PD or parkinsonism were 13% for monozygotic and 5% for same-sexed dizygotic twin pairs, with a heritability estimate of 40%. In the cross sectional analyses (based on 49,814 individuals), we identified 287 twins with PD and 79 twins with parkinsonism. Concordance rates for PD were 4% for monozygotic and same-sexed dizygotic twin pairs and 0 for opposite-sexed twin pairs. Concordance rates for PD or parkinsonism were somewhat higher but the heritability estimate was nonsignificant. Our longitudinal analyses demonstrate that PD and parkinsonism are modestly heritable.     

Early demise of twins in a cohort of stillbirths and second trimester miscarriages

Twins, particularly monochorionic (MC) pairs, are at increased risk for fetal death. Whereas previous work has sought to understand the mechanisms for this increased mortality, most studies analyze viable twin pregnancies or liveborn twin cohorts. In the Wisconsin Stillbirth Service Program cohort of 3,137 stillbirths and second trimester miscarriages, we identified 175 twin pregnancies for a twinning rate of 56/1,000, which is approximately double the general population. The excess of twins among miscarriages and stillbirths was attributable to MC pairs as the incidence of dizygotic (DZ) twinning was not increased compared to livebirth data. The leading causes of fetal demise among twins were twin–twin transfusion, acardia, and twin–twin disruption. Maternal causes of death, primarily premature rupture of membranes, were moderately increased in both MC and DZ twins relative to singletons. Although deceased twins were smaller than expected for viable twins at comparable gestational ages, placenta weights of deceased MC pairs were large compared to combined fetal weight, which indicates placental inefficiency likely due to vascular shunting. Co‐twin survival was much lower for MC than for DZ pairs. Therefore, earlier diagnosis and treatment of MC twinning complications may decrease prenatal mortality.     

Suicidal behavior in twins: a replication

OBJECTIVE: Our two previous reports showed that monozygotic (MZ) twins were significantly more concordant for both completed suicide and attempted suicide than dizygotic (DZ) twins. We wished to replicate the finding that MZ co-twins showed greater concordance for suicidal behavior. METHOD: We collected a new series of 28 twin pairs in which one twin had committed suicide. RESULTS: We found that 4 of the 13 MZ twin pairs were concordant for suicidal behavior compared with 0 of the 15 DZ twin pairs (P=0.035). CONCLUSIONS: These data confirm our previous reports that MZ co-twins show greater concordance for suicidal behavior than DZ co-twins, consistent with genetic influence.     

Are thyrogastric autoantibodies associated with an increased susceptibility to developing type 1 (insulin-dependent) diabetes? A study in identical twins

To examine whether the presence of thyrogastric autoantibodies is associated with an increased susceptibility towards developing type 1 diabetes we have tested for thyroid (microsomal and thyroglobulin) and gastric-parietal cell antibodies in 86 pairs of identical twins, 47 discordant and 39 concordant for type 1 diabetes. Autoantibodies were detected in both twins of a pair in 35 and in neither twin in 45 pairs. In only 6 pairs (3 discordant) was there a discrepancy in the antibody results between co-twins. The frequency of antibodies was similar in twin pairs discordant, (21/44, 48%), and concordant, (14/36, 39%), for diabetes. Thyrogastric antibodies were not more frequent in pairs that were female, diagnosed above the age of 20, or had HLA DR3 as opposed to DR4. We conclude that thyrogastric autoantibodies are common in both type 1 diabetic patients and their non-diabetic identical twins. Their presence appears to be genetically determined but does not increase the susceptibility of developing diabetes. The presence of autoantibodies does not appear to indicate a separate aetiological type of diabetes.     

Diagnosis and management of heterokaryotypic monochorionic twins

The diagnosis, management, and outcome of six consecutive heterokaryotypic monochorionic twins were evaluated. All suspected cases, based on discordant ultrasound findings, underwent amniocentesis of both sacs. Two cases also had chorionic villous sampling (CVS). Dual amniocentesis was superior to CVS in diagnosing heterokaryotypic monochorionic twins. In four cases, the X-chromosome was involved and autosomal aneuploidy was noted in the others. In five cases, the anomalous twin was selectively reduced by cord coagulation. All pregnancies ended with a phenotypically normal liveborn and all children are developing normally at 1-7 years of age.     

X-inactivation patterns in monozygotic and dizygotic female twins

We have tested the hypothesis that contrasting X-inactivation patterns could be a trigger for monozygotic twinning in females. X-inactivation patterns were studied in umbilical cord tissue in 43 monozygotic twin pairs and 24 dizygotic twin pairs. Very skewed or non-random X-inactivation patterns were observed in both twins in six of the monozygotic twin pairs and in one of the dizygotic twin pairs. Contrasting X-inactivation patterns occurred in only one of the six monozygotic twin pairs. This does not support the original hypothesis. There is a trend to extreme skewing of X-inactivation pattern occurring more frequently in monozygotic twins. © 1996 Wiley-Liss, Inc.     

应用微卫星DNA基因分型技术进行双生子卵型鉴定

目的 用微卫星DNA基因扫描和分型技术建立双生子卵型鉴定法。方法 选取69对同性别双生子、6对异性别双生子和17对同胞对,抽提基因组DNA,单盲设计,随机编号后,采用9对荧光标记的,在中国人群中具有高度杂合度的短串联重复序列（short tandem repeat,STR)引物,进行基因扫描和分型分析。根据这9个STR基因型的一致性来鉴别卵型。结果 9个STR基因型完全一致的63对受检者全部为同性别双生子,6对异性别双生子和17对同胞对的STR基因型均不完全一致,另有6对同性别双生子的STR基因型也不完全一致,经计算采用6个或5个STR位点判定同性别同卵双生的可信性分别大于99.6%和99%,采用全部9个位点判定同性别同卵双生的可信性大于99.95%。结论 STR基因扫描和分型技术为在基因组水平上直接判别双生子卵型,提供了一种准确,可靠的鉴定方法,它还有快速,简便等优点。     

Unexpected HLA haplotype sharing in dizygotic twin pairs discordant for rheumatoid arthritis.

Dizygotic twins are generally believed to be no more genetically similar than sibs born from separate pregnancies. In the present study, a panel of 93 dizygotic twin pairs discordant for rheumatoid arthritis were typed for HLA-A, -B, -Cw, and -DR antigens. HLA haplotype sharing identical by descent between the twins showed a trend towards increased sharing of both HLA haplotypes; this increased sharing was statistically significant when the female/female twin pairs were considered separately. In contrast, the pattern of HLA haplotype sharing in sib pairs (n = 128) was consistent with a 1:2:1 ratio of 2, 1, or 0 haplotypes shared. An analysis of 16 normal dizygotic twin pairs was consistent with these results raising the possibility that dizygotic twins in general are genetically more similar at the HLA complex than sibs born from separate pregnancies.     

Heritability of reproductive hormones in adult male twins

BACKGROUND: Proper functioning of the male reproductive axis depends on complex feedback systems between several hormones. In this study, the genetic contribution of various endocrine components of the hypothalamic-pituitary-testicular axis is evaluated and previously observed differences in FSH and inhibin B levels between mono- (MZ) and dizygotic (DZ) twins are re-investigated. METHODS: Inhibin B, FSH, LH, sex hormone-binding globulin (SHBG) and testosterone levels were assayed in 128 adult males (20 MZ twin pairs, 7 single MZ twins, 10 DZ twin pairs, 27 single DZ twins and 34 siblings of twins, constituting 10 sibling pairs), aged 15.6-68.7 years. Hormone levels were compared across zygosity groups and heritability estimates were obtained using maximum likelihood variance component analysis. RESULTS: Heritability estimates ranged from 56% (testosterone) to 81% (inhibin B and SHBG). For LH and FSH, the heritability was estimated at 68% and 80% respectively. No mean differences in hormone levels were observed across groups. CONCLUSIONS: All measured hormones are highly heritable. A difference in the FSH-inhibin B feedback system between DZ twin males and MZ twin males could not be confirmed.     

Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins

BACKGROUND: Previous twin studies of asthma and allergy implicate both genetic and environmental factors in disease risk, but few have related the occurrence of clinical disease to objective markers of allergic sensitization in twins. OBJECTIVE: We sought to investigate the concordance and interrelationships of self-reported allergic disease and total and aeroallergen-specific IgE levels within pairs of British adult female twins. METHODS: Three hundred forty monozygotic and 533 dizygotic pairs, aged 18 to 72 years, completed questionnaires about allergic disease. Of these, 282 monozygotic and 270 dizygotic pairs were tested for total IgE and specific IgE to Der p 1, mixed grass pollen, and cat dander by means of fluoroimmunoassay. RESULTS: Concordance rates for all variables were higher for monozygotic than for dizygotic twins, significantly (P < .05) so for hay fever, eczema, and specific IgE positivity but not (P > .05) for self-reported asthma or allergies. Within-pair correlations of log-transformed IgE were 0.59 for monozygotic twins and 0.29 for dizygotic twins, implying heritability of 60%. Within both monozygotic and dizygotic pairs discordant for hay fever or reported allergies, the affected twin had significantly higher total and specific IgE levels. Within pairs who were doubly discordant for 3 allergic diseases, associations between diseases were of similar strength for monozygotic and dizygotic pairs. CONCLUSIONS: These results confirm that genetic factors influence susceptibility to aeroallergen sensitization and clinical allergic disease. However, genetically identical twins are often discordant in their expression of atopy, suggesting a substantial modifying role for environmental factors.     

A genetic analysis of the Epworth Sleepiness Scale in 1560 World War II male veteran twins in the NAS-NRC Twin Registry

Responses to the eight-item Epworth Sleepiness Scale (ESS) obtained from 1560 World War II male veteran twin pairs [818 monozygotic (MZ), 742 dizygotic (DZ)] were analysed to determine the extent to which genetic influences are involved in self-reported daytime sleepiness in the elderly. Average ESS score (+/- SD) in this sample was 7.1 +/- 3.9, range 0--24. More than half of the twins (65%--67%) reported a moderate to high chance of falling asleep while lying down to rest; fewer than 3% admitted that this would occur while sitting and talking to someone or while stopped in traffic. Daytime sleepiness was not associated with age but was significantly and positively associated with obesity. The intraclass twin correlation on ESS scores was 0.39 in MZ pairs and 0.21 in DZ pairs (both P < 0.001). Structural equation modeling of the observed variance-covariance matrices for MZ and DZ twins estimated the heritability of ESS to be 38% (95% confidence interval 33%--44%). Environmental influences not shared by twin brothers accounted for the remaining variance in daytime sleepiness. A reasonable interpretation of the heritability of ESS in this healthy cohort of elderly male twins is a genetic susceptibility for disordered breathing during sleep.     

Erythropoietin in monochorionic twin pregnancies in relation to twin--twin transfusion syndrome

Fetal erythropoietin (Epo) concentrations were studied in monochorionic (MC) twin pregnancies in relation to twin-twin transfusion syndrome (TTTS). Matched maternal and fetal blood samples in utero were obtained from MC twins with TTTS (n = 15) and without TTTS (n = 6). In a second group of five sets of twin pairs with or without TTTS, immunolocalization of Epo was performed in archived paraffin wax sections of liver and kidney collected at autopsy. Epo was measured using a chemiluminescence assay and expressed as gestation independent Z-scores and given as mean +/- 95% confidence intervals (CI). Fetal Epo concentrations in utero were higher in MC twins with TTTS than the non-TTTS as a group (P < 0.001). There was no difference in Epo concentrations between TTTS and non-TTTS twin pairs. Fetal Epo concentrations were correlated with pO(2) in the recipient (r = 0.64; P < 0.01), donor (r = 0.64; P < 0.01) and control twins (r = 0.76; P < 0.01). Immunostaining of the fetal kidney localized Epo primarily to the cytoplasm of the proximal convoluted tubules. The intensity of staining in the kidney and liver was comparable between TTTS and non-TTTS twin pairs. Fetal Epo concentrations were higher in the TTTS than non-TTTS twin pairs and were correlated with the degree of hypoxaemia. However, Epo concentrations were comparable between donor and recipient twins, perhaps due to similar production rather than inter-twin transfusion of blood.     

Risk factors for asthma in young adults: a co-twin control study

Background: The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8‐year period. Methods: From the birth cohorts 1953–1982 of the Danish Twin Registry, 6090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire‐based study in 1994 participated in a similar follow‐up study in 2002. Subjects were regarded incident asthma cases when responding affirmatively to the question ‘Do you have, or have you ever had asthma'? in 2002. Pairs in which only one twin developed asthma – discordant pairs – were identified and conditional logistic regression was applied to detect effects of risk factors. Results: A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3.16, 95% CI: 1.29–7.73, P = 0.007) and exercise (OR for inactivity = 0.35, 95% CI: 0.13–0.91, P = 0.023) were significantly associated with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44–4.13, P = 0.001), eczema (OR = 1.96, 95% CI: 1.02–3.78, P = 0.040), female sex (OR between males and females = 0.54, 95% CI: 0.36–0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02–1.20, P = 0.009) were significant predictors of asthma. Conclusions: Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma.     

Erythrocyte catechol-O-methyltransferase activity in psychotic twins

Erythrocyte catechol-O-methyltransferase (COMT) activity was analyzed in 20 twin pairs, 6 monozygotic and 14 dizygotic, where one or both twins showed psychotic or prepsychotic symptoms. Fifteen of these pairs, 4 monozygotic and 11 dizygotic, were diagnosed as discordant for serious mental disturbance. The different psychotic states within twins did not seem to be associated with any difference in COMT activity.     

Electron microscopic study of distinctive structures in peripheral blood lymphocytes obtained from twins with systemic lupus erythematosus.

Peripheral blood lymphoid cells obtained from nine twin pairs (six monozygotic and three dizygotic) in which one or both twins had systemic lupus erythematosus (SLE) were examined by electron microscopy for the occurrence of two distinctive intracytoplasmic structures-tubuloreticular structures (TRS) and tubular crystalloids (TC). TRS were found in 0.8 to 14.8% of lymphoid-cell cross sections in 9 of 11 twins with SLE and 2 clinically well but serologically abnormal twins. Lymphoid cells of twins both clinically and serologically normal did not exhibit TRS, although their monozygotic or dizygotic SLE-positive counterparts possessed these structures. Thus, the expression of TRS was more consistent with an acquired than inborn trait and appeared to correlate with disease and serologic manifestations of SLE. TC were found in 1.7 to 7.9% of lymphoid-cell cross sections in every twin examined. No correlation was recognized between clinical or laboratory data and the frequency of TC-bearing cells. The significance and the ultrastructural development of TC in the peripheral blood lymphoid cells are briefly discussed.     

Genetic and environmental influences on insomnia, daytime sleepiness, and obesity in twins

STUDY OBJECTIVES: To better understand the relationships of insomnia, sleepiness, and obesity. DESIGN: Classic twin study. SETTING: A community-based twin registry in Washington State. PATIENTS OR PARTICIPANTS: One thousand forty-two monozygotic and 828 dizygotic twin pairs participating in the University of Washington Twin Registry. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Twins were, on average, 32 years old; 61% were women, and 19.5% were obese, defined as a body mass index > or = 28. Insomnia and sleepiness were endorsed by 19.3% and 3.7% of twins, respectively. Twin correlations were higher in monozygotic than dizygotic twins for insomnia (0.47 versus 0.15), sleepiness (0.37 versus 0.14), and obesity (0.82 versus 0.46). Heritability estimates were 57% for insomnia (p < .001; 95% confidence interval 47-63), 38% for sleepiness (p < .01; 95% confidence interval 16-46), and 73% for obesity (p < .001; 95% confidence interval 49-87). Multivariate genetic model fitting revealed that common additive genetic effects comprised 12.8% of the phenotypic correlation between insomnia and sleepiness (p < .01) and 10% of the phenotypic correlation between insomnia and obesity (p < .01). The phenotypic correlation between sleepiness and obesity was not due to common additive genetic effects. CONCLUSIONS: Insomnia, sleepiness, and obesity are under strong genetic influence. Common genetic effects were observed between insomnia and both sleepiness and obesity, suggesting shared genetic contributions to these phenomena.