Contribution of familial factors to the occurrence of cancer before old age in twin veterans

In an earlier report, we evaluated familial factors in deaths from all causes before age 62 among the 31,848 white male twin veterans who were followed during 1946–1978 through the National Academy of Sciences-National Research Council Twin Registry. We now report data for this group on twin concordances and heritabilities of cancer recorded on the death certificate as an underlying or associated cause. The study subjects have a mortality from cancer 0.88 times, and one from all causes 0.84 times, that of U.S. white males [12], but this is very similar to the mortality of other U.S. veterans [9].

Among 11,350 monozygotic (MZ) and 14,450 dizygotic (DZ) individuals in twin pairs alive on January 1, 1946, 1,162 MZ and 1,646 DZ individuals died before January 1, 1979. Cancer was diagnosed for 223 MZ and 323 DZ twins as an underlying or associated cause of death. Among the latter were 176 MZ and 274 DZ pairs with the only death in the pair a cancer death, 10 MZ and eight DZ pairs concordant for cancer, and 12 MZ and 14 DZ pairs in which the first death in the pair from cancer was followed by death of the other twin from another cause. When account is taken of the three MZ and two DZ pairs concordant for lung cancer, most likely related to cigarette smoking, the twin cancer death concordance rates are very low, and they are not appreciably different between the two zygosity groups.

Genetic factors may be important in some specific forms of cancer. However, these data suggest that genetic factors and early familial environment, generally shared by twin-pair members, do not contribute much to mortality from most cancers between 30 and 60 years of age.

     

Genetic influences in self-reported symptoms of obstructive sleep apnoea and restless legs: a twin study.

Sleep disorders, such as obstructive sleep apnoea (OSA) and restless legs syndrome (RLS), are very common. The relative importance of genetic and nongenetic (environmental) influences on the symptomatology of these conditions has not been well studied. This study uses the twin design to examine this by evaluating OSA and RLS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. Six thousand six hundred unselected female twin pairs, identified from a national volunteer twin register, were asked to complete a medical questionnaire. This questionnaire included questions on OSA and RLS symptoms, as well as questions on subject demographics, past medical history, smoking history and menopausal status. Responses were obtained from 4503 individuals (68% response rate). A total of 1937 twin pairs were evaluable: 933 MZ pairs (mean [range] age 51 [20-76] years) and 1004 DZ pairs (age 51 [20-80] years). Concordance rates were higher for MZ than DZ twins for OSA and RLS symptoms. Multifactorial liability threshold modeling suggests that additive genetic effects combined with unique environmental factors provide the best model for OSA and RLS symptoms. Heritability was estimated to be 52% (95% confidence interval 36% to 68%) for disruptive snoring, 48% (37% to 58%) for daytime sleepiness, 54% (44% to 63%) for restless legs, and 60% (51% to 69%) for legs jerking. These estimates dropped only slightly after adjustment for potential confounding influences on the symptoms of snoring and daytime sleepiness. These results suggest a substantial genetic contribution to the symptomatology of OSA and RLS. More research is needed to identify the genes responsible, and may ultimately lead to new therapies.     

学龄双生子儿童头面部特征的遗传学分析

为探讨遗传与环境因素对学龄双生子儿童头面部特征的影响, 对呼和浩特市和包头市7-12岁369对双生子儿童(同卵180对, 同性别异卵141对, 异性别异卵48对)的16项头面部指标进行活体测量。采用通径分析方法, 用Mx软件拟合最佳结构方程模型, 计算各指标遗传与环境方差组分, 分析年龄、性别的作用。结果发现, 校正年龄后, 头部指标中头围的遗传度(男66%, 女66%)较高; 面部指标中, 容貌面高的遗传度(男73%, 女84%)最高, 其次为鼻宽(男57%, 女67%)、眼内角间宽(男57%, 女50%)和额最小宽(男50%, 女50%); 头长(男64%, 女25%)、头宽(男26%, 女82%)、眼外角间宽(男76%, 女34%)和容貌耳长(男23%, 女70%)的遗传度存在一定的性别差异。表明遗传因素与环境因素对学龄双生子儿童的头面部发育均有一定影响, 其中遗传因素对男女头围及容貌面高、男性头长和眼外角间宽、女性头宽、鼻宽、口宽、容貌耳长的影响相对较大。     

Genetic influence on human lifespan and longevity

There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20–30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003–2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.     

Sex difference in heritability of BMI in South Korean adolescent twins

Twin studies of BMI on the basis of Asian twins are extremely rare. Eight hundred eighty-eight pairs of twins [279 monozygotic (MZ) and 82 dizygotic (DZ) pairs of male twins, 319 MZ and 82 DZ pairs of female twins, and 126 opposite-sex pairs of DZ twins] completed items concerning height and weight through a mail and a telephone survey. A general sex-limitation model was applied to the data. Heritability estimate was greater among women than among men. However, there was little evidence of sex-specific genes. Under the best-fitting model, additive genetic variances were 82% [95% confidence interval (CI): 72% to 95%] for men and 87% (95% CI: 77% to 99%) for women; shared environmental variances were negligible in both men and women. These estimates of genetic and environmental factors in BMI found among South Korean adolescent twins were broadly in the range of those reported in previous studies of BMI based on Western twin samples.     

Fourier analysis of facial profiles of young twins

Twins studies provide a powerful approach to determining the relative contribution of genetics and environment to observed variation. Such studies assume trait differences in monozygous (MZ) twins are due to environmental factors and those in dizygous (DZ) twins are due to both genetic and environmental factors. This study quantitated facial profiles of twins using Fourier equations, determining their value in profile analysis and the assessment of the genetic contribution to facial shape. Standardized profile slide photographs of 79 pairs of 4-6 year-old twins (37 MZ pairs, 42 DZ pairs) were scanned and x and y coordinates were extracted from each profile using sellion and Camper's plane as references. The coordinates were subjected to Fourier analysis and the normalised vertex projection coefficients were studied. The means of the differences between coefficients for MZ co-twins did not differ significantly from that of DZ co-twins, although the DZ group showed higher mean differences in the higher harmonics. Subjective examination of superimposed reconstructions showed wider variation between DZ co-twins than MZ co-twins. Correct classification of twins by discriminant function analysis using Fourier coefficients was similar for both groups (MZ: 70.3%; DZ: 73.8%). Fourier analysis could quantitate facial profiles of young children and differentiate some details, but was unable to discriminate between genetic and environmental influences, and any possible interactions between these influences, on their overall facial profiles at this developmental stage.     

Happy families: a twin study of humour.

The objective of this study was to estimate how much of an individual's appreciation of humour is influenced by genetic factors, the shared environment or the individual's unique environment. A population-based classical twin study of 127 pairs of female twins (71 monozygous (MZ) and 56 dizygous (DZ) pairs) aged 20-75 from the St Thomas' UK Adult Twin Registry elicited responses to five 'Far Side' Larson cartoons on a scale of 0-10. Within both MZ and DZ twin pairs, the tetrachoric correlations of responses to all five cartoons were significantly greater than zero. Furthermore, the correlations for MZ and DZ twins were of similar magnitude and in some cases the DZ correlation was greater than that of the MZ twins. This pattern of correlations suggests that shared environment rather then genetic effects contributes to cartoon appreciation. Multivariate model-fitting confirmed that these data were best explained by a model that allowed for the contribution of the shared environment and random environmental factors, but not genetic effects. However, there did not appear to be a general humour factor underlying responses to all five cartoons and no effect of age was seen. The shared environment, rather than genetic factors, explains the familial aggregation of humour appreciation as assessed by the specific 'off the wall' cognitive type of cartoons used in this study.     

The influence of zygosity and chorion type on fat distribution in young adult twins consequences for twin studies.

An adverse intra-uterine environment has been associated with abdominal fat distribution in singletons. Twins often have a low birth weight and a short gestation. Therefore, they may have an increased risk to develop abdominal obesity. Furthermore, monozygotic monochorionic twins (MZ MC) have a larger intra-pair birth weight difference compared to monozygotic dichorionic twins (MZ DC). If adult anthropometry is programmed in utero, this may affect the intra-pair correlations in adulthood and, consequently, also the results from the classic twin method to estimate genetic and environmental influences. In the present study, we compared the absolute values, the intra-pair differences, and the intra-pair correlations of body mass, height, BMI, and abdominal fat distribution of 424 MZ MC, MZ DC and dizygotic (DZ) twin pairs (aged 18-34 yrs). DZ, MZ DC and MZ MC twins did not differ for most anthropometric characteristics. Only MZ women tended (p = 0.03) to accumulate more abdominal fat compared to DZ twins. Overall, the contribution of zygosity and chorion type to adult anthropometry was rather low (< or = 1.7%). Although the intra-pair birth weight difference of MZ MC pairs (10.5% in men, 12.3% in women) was significantly larger compared to that of MZ DC pairs (6.9% and 9.2% resp.), the intra-pair differences in adult anthropometry were similar for both MZ twin types. Also the intra-pair correlations of MZ MC and MZ DC pairs were strikingly alike, suggesting no significant influence of the prenatal environment on adult concordance. In conclusion, the substantial difference in the prenatal environment of MZ MC and MZ DC twins did not result in a difference in intra-pair concordance of adult anthropometry and fat distribution. Therefore, we suggest that the chorion type of MZ twins does not bias the twin design and the estimation of the genetic contribution to adult anthropometry.     

Genetic and environmental influences of surfactant protein D serum levels

The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms defining the constitutional serum level of SP-D and determine the magnitude of the genetic contribution to serum SP-D in the adult population. Recent studies have demonstrated that serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located in the NH(2)-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation among serum SP-D and metabolic variables. The Met11Thr variant explained a significant part of the heritability indicating that serum SP-D variance could be decomposed into non-shared environmental effects (e(2) = 0.19), additive genetic effects (h(2) = 0.42), and the effect of the Met11Thr variations (q(2) = 0.39).     

Color perception in twins

The classical twin method was used to examine the genotype--phenotype relationship in color vision. Suprathreshold color differences were assessed by 5 pairs of monozygotic (MZ) and 3 pairs of dizygotic (DZ) twins. The control group included 3 unrelated normal trichromats, a non-twin sibling pair, and a previously diagnosed deuteranomal. Concordance rates were calculated by Spearman's correlation coefficients (rs) and Procrustean distances (gl) between the reconstructed color spaces for each related pair of observers. For 4 pairs of the MZ twins, the rs values were comparable to intraindividual variability in the control normal trichromat; they were significantly higher (0.94-0.97) than those for the DZ twins and siblings (0.72-0.82). The gl values for the MZ twins (0.008-0.029) were lower than for the DZ twins (0.073-0.079) and siblings (0.053). The high concordance between each pair of the MZ twins suggests that their shared photopigment genome constrains a contribution of possible individual variations in nongenetic factors to variability of their color spaces. Lower concordance rates in the DZ twins and siblings can be attributed to differences in the inherited arrays of photopigment genes. Contributions to intrapair variation in color spaces of twins from cognitive factors such as perceptual-cognitive color categorization and decision-process variability are discussed.     

A twin study of structural chromosome aberrations in lymphocytes

Structural chromosome aberrations were analyzed in peripheral lymphocytes of eight monozygotic (MZ) and seven dizygotic (DZ) pairs of male twins. There was no significant intrapair difference in the variance of aberration frequencies among the MZ and DZ twins. Thus, there was no evidence of a major genetic influence on the development of structural chromosome aberrations. Although a genetic component could not be excluded, it was concluded that any chromosome aberrations observed were probably due mainly to environmental influences.     

A study of lactose absorption capacity in twins

Summary Lactose absorption capacity was determined by lactose tolerance tests with breath hydrogen determination in 102 healthy, adult, Hungarian pairs of twins in order to test monogenic Mendelian inheritance of the absorptive lactase phenotypes, lactose absorber and lactose malabsorber. Of the total, 52 pairs were monozygous (MZ) and 50 dizygous (DZ) twins of indentical sex. All MZ twins were concordant with respect to lactase phenotype. Among DZ twins, the distribution of lactase phenotypes was in agreement with Hardy-Weinberg expectations derived from the frequencies of the hypolactasia gene in DZ and MZ twins, and in the general Budapest population.In the second part of the study, three commonly used methods of lactose tolerance testing, the blood glucose, the blood galactose, and the breath hydrogen tests, were compared in 49 pairs of twins concordant for lactase phenotype. Blood galactose concentration showed the greatest and only significant difference between the intrapair correlation coefficients of MZ and DZ, and no overlap between lactose absorbers and lactose malabsorbers. The intrapair correlation coefficients of peak breath hydrogen concentration in MZ and DZ twins did not significantly differ from zero, but the resolution of lactase phenotypes was satisfactory. Differences in glucose absorption and concentration in lactose absorbers and malobsorbers overlapped considerably, and among lactose absorbers correlation coefficients in DZ were higher than in MZ twins. In MZ and DZ twins, the difference in concordance and constancy of lactose intolerance symptoms was not significant.     

Models for the longitudinal genetic analysis of same-age twins: application to HDL cholesterol.

Models are presented for the analysis of longitudinal data from same-age twins which permit the exploration of a remarkably diverse array of alternative explanations for continuity and change during development. Data of this type permit the detection of new sources of genetic or environmental covariation during development that are not expressed at earlier ages and, because they include the effects of age-specific genes, the resulting heritability estimates are more reliable than those obtained from relatives who differ in age. The proposed models were applied to measurements of HDL cholesterol obtained on 81 pairs of monozygotic (MZ) twins and 69 dizygotic (DZ) pairs at 11, 12.5 and 14 years of age. All three MZ co-twin correlations were substantially higher than the self correlations across occasions, suggesting that new sources of genetic or environmental covariation must be expressed during early adolescence. This interpretation was confirmed by analysis of the full covariance matrices which showed that only models which assumed the expression of new or age-specific genes could explain the observed pattern of covariation. Because they include the effects of age-specific genes, the resulting heritabilities (0.80-0.83) were substantially higher than many previous estimates.     

Familial resemblance for anthropometric traits in dizygotic twins and siblings

Familial resemblance for fifty anthropometric traits was studied on a sample of 45 MZ, 101 DZ twin pairs and their 125 singleton siblings. Intraclass correlation coefficients were significant for all the traits. However, resemblance within DZ twin pairs was significantly greater than within sibs for 22 variables, showing that the former had a more correlated environment than the latter. The study also showed that head and facial traits were relatively more stable to the environmental factors than the body traits and hence more suitable for cross-cultural comparisons. The study listed measures of girth and skinfold, thickness as the most labile traits.     

双生子骨龄、身高及体重的研究

本文对307对同性别双生子的骨龄、身高和体重进行了研究。结果表明,骨龄、身高和体重均受遗传因素影响。遗传因素对不同年龄阶段的影响程度可能是不同的。长时间的不同环境因素对身高和体重的影响较骨龄更大。     

The East Flanders Prospective Twin Survey (Belgium): a population-based register.

The East Flanders Prospective Twin Survey (EFPTS), started in 1964, is unique among the 17 major European twin registers because it is population based, the twins (and higher order births) are ascertained at birth, basic perinatal data are collected, chorion type is established and, when appropriate, genetic markers including DNA fingerprints, are determined. The total number of sets is 5089 twin, 158 triplet and 14 of higher order. Zygosity has been diagnosed on the basis of sex, placental structure and genetic markers in more than 95% of pairs. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic-diamnionic pairs (early), the monochorionic-diamnionic pairs (intermediate), and the monochorionic-monoamnionic pairs (late). Methodology and basic results in twins are considered in this article; detailed studies will be reported later. The sex proportion in dizygotic (DZ) twins is the same as in singletons, whereas monozygotic (MZ) twins number more girls than boys. The difference in perinatal mortality between DZ and MZ twins is limited to the monochorionic MZ subgroup. Birth weight is highest in DZ twins and diminishes stepwise in MZ dichorionic and MZ monochorionic twins. Duration of pregnancy follows the same trend but is limited to a few days. Iatrogenic pregnancies are increasing to the point of representing almost 50% of the twin births in 1997.     

The Host Genotype and Environment Affect Strain Types of Bifidobacterium longum subsp. longum Inhabiting the Intestinal Tracts of Twins

To investigate the influences of host genotype and environment on Bifidobacterium longum subsp. longum inhabiting human intestines at the strain level, six pairs of twins, divided into two groups (children and adults), were recruited. Each group consisted of two monozygotic (MZ) twin pairs and one dizygotic (DZ) twin pair. Child twins had been living together from birth, while adult twins had been living separately for 5 to 10 years. A total of 345 B. longum subsp. longum isolates obtained from 60 fecal samples from these twins were analyzed by multilocus sequence typing (MLST), and 35 sequence types (STs) were finally acquired. Comparison of strains within and between the twin pairs showed that no strains with identical STs were observed between unrelated individuals or within adult DZ twin pairs. Eight STs were found to be monophyletic, existing within MZ twins and child DZ twins. The similarity of strain types within child cotwins was significantly higher than that within adult cotwins, which indicated that environment was one of the important determinants in B. longum subsp. longum strain types inhabiting human intestines. However, although these differences between MZ and DZ twins were observed, it is still difficult to reach an exact conclusion about the impact of host genotype. This is mainly because of the limited number of subjects tested in the present study and the lack of strain types tracing in the same twin pairs from birth until adulthood.     

Interaction between the ABO and Rh-Hr blood group systems in pairs of monozygotic (MZ) and dizygotic (DZ) twins

Previous studies have revealed significant deviations of twin pairs' blood group distributions. A comparison between monozygotic (MZ) and dizygotic (DZ) pairs in a sample of 688 twin pairs as to interaction between ABO and Rh indicates that the main contribution to total deviation comes from the MZ pairs, thus confirming a different behaviour of the two twin types in this respect.     

Inheritance of hypodontia in twins

The aim of this study was to establish prevalence of hypodontia in the twin sample and to assess the degree of its heritability. A study was performed in a sample of 96 twin pairs, 38 pairs being monozygotic (MZ) and 58 pairs dizygotic (DZ), from north-west Croatia. The sample included 25.82% of all twins born in the region during a ten-year period. The twin zygosity was determined according to the WHO recommendations (1996). A revised Holzinger's index (Hc') according to Allen was applied to calculate the degree of heritability. Hypodontia was found in 22 out of the total of 192 twins analyzed (11.5%). Among 96 pairs of twins, hypodontia was observed in 17 pairs (7 MZ and 10 DZ pairs). Among the MZ, 4 pairs were found to be concordant for hypodontia, among the DZ one pair only. The heritability index was 0825. A prevalence of hypodontia in twins observed in this study is significantly higher than in the general population. A high index of heritability (Hc' = 0.825) points to a high genetic determination.