The association between body height and coronary heart disease among Finnish twins and singletons

OBJECTIVE: An inverse association between body height and the incidence of coronary heart disease (CHD) has been observed. However, the mechanisms behind this association are still largely unknown. We will examine the role of genetic and familial factors behind the association in a large twin data set. DESIGN AND SETTING: The data were derived from the Finnish Twin cohort including 2438 singletons, 4073 monozygotic (MZ) twins, and 9202 dizygotic (DZ) twins aged 25-69 years at baseline in 1976. Incident CHD cases were derived from hospital discharge data and cause of death data between 1977 and 1995. Cox regression analysis and conditional logistic regression analysis were used. RESULTS: In population-level analyses no differences in the general risk of CHD between zygosity groups were found. The association between body height and CHD was similar between sexes and zygosity groups. When men and women in all zygosity groups were studied together an increased risk of CHD was found only among the shortest quartile (hazard ratio [HR] = 1.34, 95% CI: 1.14-1.57). Among the twin pairs discordant for CHD a suggestive increased risk for the shorter twin was seen among DZ twins (odds ratio [OR] = 1.19, 95% CI: 0.95-1.48) when men and women were studied together. CONCLUSION: An inverse association between body height and CHD was broadly similar between sexes and twin zygosity groups and was associated with short stature. Among discordant twin pairs we found a weak association among DZ twins but not MZ twins. This may suggest the role of genetic liability behind the association between body height and CHD.     

Plasma cholesterol variation in the National Heart, Lung and Blood Institute Twin Study

Plasma cholesterol was measured in the fifth decade of the life of 249 pairs of monozygotic (MZ) and 262 pairs of dizygotic (DZ) World War II veteran twins and 70% of the same cohort 10 years later. There were no significant differences between the mean cholesterol values for MZ and DZ twins, and the within DZ pair mean squares were significantly larger than the within MZ pair mean squares for all of the cholesterol variables measured. However, the DZ twins were found to have greater total variance, positive skewness, and leptokurtosis than the MZ twins for total and high-density lipoprotein cholesterol, and the total/high-density ratio. Comparisons with published data revealed that the variance of DZ twins was similar to that of singletons while the MZ twins have smaller total variance, perhaps owing to a missing component of variation. Hypotheses for the source of the differences in the zygosity distributions are proposed including environmental influences (pre- or post-natal and within- or among-families), genetic differences, and selection at the time of induction into the armed services. Because of the differences in total variance of the two zygosities it is difficult to know which estimates of genetic variance or heritability have the least bias. However, these data provide clues that may lead to further understanding of sources of plasma cholesterol variation that could be important to the future understanding of risk for coronary heart disease.     

Socioeconomic position and twins' health: a life-course analysis of 1266 pairs of middle-aged Danish twins

BACKGROUND: The association between socioeconomic circumstances and health in adulthood could come about through processes that may be divided into factors experienced early in life and those experienced in later adulthood. In order to disentangle the influences on health of the early genetic, prenatal and rearing environmental factors from environmental factor later in life, we compared the health status among male and female twin pairs who lived together during childhood and were discordant or concordant on adult socioeconomic position. METHODS: A cross-sectional survey among a random sample of middle-aged Danish twins was conducted in 1998-99. The study population included 1266 like-sex twin pairs [52.5% monozygotic (MZ) and 47.6% dizygotic (DZ)]. Data were obtained on childhood and adult social class and on height, BMI, grip strength, depression symptoms, self-rated health, cognitive function, physical activity, smoking, alcohol and food intake. RESULTS: The expected associations between the individual twins' adult social class and health measures were observed. Among DZ male twins discordant on adult social class, the higher social class twin was on average significantly taller and had higher cognitive test scores. Among DZ female twins discordant on adult social class, the higher social class female twin was more physically active and had a higher cognitive test score. There were no significant health disparities or behavioural differences between the members of MZ twin pairs discordant on adult social class. For most health outcomes, the variability within twin pairs was related to zygosity (higher for DZ than for MZ) but not to social class. CONCLUSION: This study suggests that the relationship between adult social class and health outcomes in Denmark is due mainly to selection effects rather than a causal effect of social class exposures on health and behaviour.     

Heritability of body mass index in pre-adolescence, young adulthood and late adulthood

Increased body mass index (BMI) is a worldwide health issue. Individual differences in the susceptibility to increased BMI could be related to genes or environment. We performed a systematic review of genetic studies on BMI in pre-adolescence, young adulthood and late adulthood. We searched PubMed and EMBASE with heritability, body mass index, BMI, weight, height, anthropometry and twins as search terms. Studies reporting intra-pair correlations of healthy twin pairs that were raised together were included. This resulted in the inclusion of 8,179 monozygotic (MZ) and 9,977 dizygotic (DZ) twin pairs from twelve published studies in addition to individual participant data for 629 MZ and 594 DZ pairs from four twin registries. Structural equation modelling with intra-pair twin correlations showed that the heritability of BMI remained high over all age categories ranging from 61% (95% CI 54-64%) to 80% (95% CI 76-81%) for male and female subjects combined, while unique environmental influences increased from 14% (95% CI 13-15%) to 40% (95% CI 37-43%) with increasing age. Heritability of BMI remains consistently high over different age categories. Environmental changes over time do not seem to have as big a relative impact on an individual's weight as previously reported, suggesting a mainly genetic influence on variation in BMI over the years.     

青春前期双生子血清骨碱性磷酸酶活性测定及遗传度分析

目的 通过对青春前期双生子血清骨碱性磷酸酶(bone alkaline phosphatase,BALP)活性的测定,分析血清BALP活性的遗传度,评价特定人群钙的缺乏状况和机体对钙的需求情况.方法 调查9～16岁双生子73对,利用骨源性碱性磷酸酶试剂盒进行血清BALP活性测定.在DNA卵型鉴定基础上.以组内相关系数法及Christian遗传度计算公式分析血清BALP活性的遗传度. 结果 经卵型鉴定,73对双生子中同卵双生子34对,异卵双生子39对;BALP>250 U/L的人占43.1%,BALP为200～250 U/L占54.8%,BALP≤200 U/L占2.1%;男性中钙摄入不足者占48.4%,女性中占39.0%;各年龄组钙的摄入能满足机体需求的均不到10.0%;尤其是10～13岁年龄段儿童,明确缺钙者所占比例均>45.0%;不同性别、不同年龄间BALP均值差异无统计学意义,性别t=1.633,P=0.105;年龄F=0.323,P=0.924.经过遗传度分析,单卵双生(MZ)对内方差=191.54,对间方差=1462.22,相关系数=0.77;双卵双生(DZ)对内方差=491.03,对间方差=1475.57,相关系数=0.50;BALP活性的遗传度为0.54. 结论 青春前期的双生子普遍存在缺钙问题;BALP的活性遗传因素占54%,环境因素占46%.     

Male factor infertility: a twin study

There is a considerable body of literature on the causes of female infertility, but far less is known about male factor infertility. We conducted a classical twin study to estimate the genetic influence on 12-month male factor infertility. The study used the Vietnam Era Twin (VET) Registry, which includes male twin pairs born between 1939 and 1957, and who served in the US military between 1965 and 1975. In 1987, a health survey was mailed to all twins and obtained a 74% response rate. The current analyses comprised 1795 complete pairs in which both twins were married only once. Proband-wise concordance rates, tetrachoric correlations, and a bivariate probit model were used to calculate estimates of familial clustering and heritability for male factor infertility. The proband concordance rate for male factor infertility was 38% [95% CI 32.8, 42.4] in monozygotic (MZ) pairs and 33% [95% CI 28.0, 38.6] in dizygotic (DZ) pairs. The tetrachoric correlations for male infertility were 0.15 in MZ and 0.04 in DZ pairs. This pattern provides evidence of familial clustering, although genetic influence was not evident (P = 0.21). The current study identified that 12-month male factor infertility clustered within families. However, results suggest that factors unique to individual twins may play a more prominent role in male infertility than additive genetic effects or the common environment.     

Lifestyle factors in monozygotic and dizygotic twins

In examining genetic influences on biological variables using twins, it may be important to examine the distribution between and within twin pairs of demographic and lifestyle factors that may themselves affect the biological variable being studied. We explored the distribution of demographic and lifestyle factors that may affect blood lipid levels or ischaemic heart disease (IHD) risk among a sample of 106 monozygotic (MZ) and 94 like-sex dizygotic (DZ) twin pairs. In our sample, MZ twins were statistically significantly different from DZ twins only in marital status, cigarette smoking habits, and the ratio of polyunsaturated to saturated fat (P:S ratio) in their dietary intake. The latter variable was among many dietary variables examined (using 4-day weighed food diaries), and the size of the difference in intake was small. When comparisons were made of the similarities within twin pairs, we found members of MZ twin pairs to be statistically significantly closer than DZ twins in educational achievement, occupation, cigarette smoking, and exercise habits, and the number of days a week on which alcohol was consumed. These last three variables were consistently closer among twins with closer contact than among those with a smaller degree of current shared environment. For 12 of the 13 nutrients examined, the within-pair correlations were higher for MZ than for DZ twins, although our test for significant genetic variance showed statistical significance only for intake of complex carbohydrates. We conclude that MZ twins share demographic and lifestyle factors that might influence the risk of IHD and blood lipid levels to a greater degree than do DZ twins, although it is difficult to say if these similarities in lifestyle result from genetic influences or not. Nevertheless, ascribing differences between correlations in MZ and DZ twin pairs for lipid levels as being purely "genetic"--as implicit in conventional measures of heritability--is likely to overestimate the influence of genetic factors.     

Influence of genetic and environmental factors on the immunogenicity of Hib vaccine in Gambian twins

The differences in incidence rates of Haemophilus influenzae type b disease and the variation in Hib conjugate vaccine efficacy achieved among different ethnic groups suggest genetic influences on the immune response to Hib vaccine. The serum anti-PRP antibody concentration of 43 monozygotic (MZ) and 147 dizygotic (DZ) twin pairs in the Gambia was measured using a standardised Hib ELISA. Intrapair correlations for MZ and DZ twin pairs were compared and heritability in antibody responses to Hib conjugate vaccine was estimated to be 51% (95% CI: 32-66%), indicating a significant genetic contribution in the response. We conclude that genetic factors may be involved in the variation in immune response to Hib vaccine observed in different populations and may contribute to cases of vaccine failure.     

The epidemiology of anencephaly and spina bifida in Izmir, Turkey, in the light of recent aetiological theories

The data from this study suggest that, in western Turkey, potato consumption and water hardness do not play a significant role in the aetiology of anencephaly and spina bifida (ASB). Several of the predictions of the fetus-fetus interaction theory are not supported. Other predictions could not be tested because of lack of information on the dizygotic (DZ) twinning rate. Twin data from this study, together with previous material containing explicit information on zygosity, suggest that true concordance of a particular neural tube anomaly occurs only in monozygotic (MZ) twins. It also seems that even ASB concordance occurs in DZ twins only at a rate comparable with recurrence in siblings. This confirms the earlier refutation (Field and Kerr, 1974) of the supposition of Nance (1971) that MZ twin pairs are strikingly discordant for ASB compared with DZ pairs. However, the evidence seems to go further than Field's assertion that MZ and DZ pairs are affected about equally. Concordance in DZ twins is in comparison with sibling data, but MZ pairs show a significantly higher rate of concordance in both categories. Finally, the incidence of ASB in Izmir compared with the areas of ethnic origin of the Turks, and the high representation of families from Balkan areas where the incidence more closely resembles that of Izmir, suggest that the genetic factor is important in this area.     

双生子艾森克人格与血液生化指标的相关性研究

[目的 ]了解双生子艾森克人格特点及遗传因素对艾森克人格的影响 ,探讨血液生化指标与艾森克人格的相关性。 [方法 ] 2 0 0 1年 12月对青岛市 89对 2 4岁以上的双生子 (同卵 5 5对 ,异卵 3 4对 )进行艾森克人格测试 ,检测 3 7项血液生化指标 ,并进行相关分析。 [结果 ]同卵双胞胎之间在N(情绪稳定性 )因子的相关系数高于异卵双胞胎 ,N因子的遗传度为 0 45。人格因素中只有N因子与几项生化指标有相关关系 (r <0 3 0 )。 [结论 ]艾森克人格因素中的N因子受遗传作用的倾向较大 ,血液生化指标水平并不决定人的个性心理特征。     

A genetic and environmental analysis of a twin family study of alcohol use,anxiety, and depression

Alcohol consumption, anxiety, and depression were measured by questionnaire in 572 twin families ascertained from the Institute of Psychiatry (London) normal twin register, each family consisting of an adult twin pair, their parents, and siblings-a total of 1,742 individuals. A multivariate normal model for pedigree analysis was applied to each variable, with power transformations fitted to maximise the fit with distributional assumptions. The effect of shared twin environment was estimated by considering the measured cohabitation history of twin pairs. For log-transformed alcohol consumption, amongst current drinkers this effect was the same for MZ and DZ pairs but depended on the cohabitation status of pairs. For both anxiety and depression the effect was clearly not the same for MZ and DZ pairs. Therefore the basic assumption of the classical twin method appears to be invalid for all three traits. Estimates of heritability derived from these analyses were compared with those obtained (1) by applying the classical twin method to twin data only, and (2) by a pedigree analysis ignoring the effect of shared twin environment. For all variables there were considerable differences between estimates based on the three models. This study illustrates that data from twins and their relatives which includes information on cohabitation history might distinguish shared genes and shared environment as causes of familial aggregation. In these behavioral traits the effect of shared twin environment may depend on zygosity and play a major role in explaining familial aggregation in twin family data.     

双生子的血清脂质和脂蛋白遗传度及影响因素分析

目的　分析儿童、青少年的血脂指标遗传度及影响因素。方法　选择 5～ 19岁双生子2 36对 ,平均年龄 (11 2± 3 4 )岁 ,其中同卵双生子 14 3对 ,异卵双生子 93对。在DNA卵性鉴定基础上 ,以组内相关系数法及Falconer公式计算调整年龄性别前后的遗传度 ,偏态数据进行对数转换 ;校正年龄性别 ,分析相关体格、生化指标对血脂的影响。结果　同卵与异卵双生子间甘油三酯对内方差及相关系数的差异均无显著性 ;总胆固醇、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)和脂蛋白 (a)对内方差及相关系数的差异有显著性 ,遗传度估计值分别为 0 5 6、0 5 5、0 4 9和 0 5 8,调整年龄性别后各指标估计遗传度分别为 0 6 3、0 6 3、0 5 5和 0 6 4。总胆固醇、HDL C、LDL C和脂蛋白(a)与年龄呈负相关 ;女孩的总胆固醇、HDL C、LDL C稍高于男孩。校正年龄性别后除脂蛋白 (a)外各血脂指标多数与体重指数、体脂率及培利迪西指数相关 ,与血压、血糖和血钙等也有相关性。结论　总胆固醇、HDL C、LDL C和脂蛋白 (a)受遗传因素影响较大 ,而甘油三酯主要受环境因素影响。儿童的血脂水平受年龄和性别的影响 ,与反映体脂和机体营养发育的指标相关。     

儿童青少年双生子瘦素遗传度估计及影响因素分析

目的 分析影响儿童青少年瘦素的遗传因素和环境因素,探讨性别、年龄和体质量指数(BMI)的作用,为儿童肥胖早期预防提供依据.方法 选择6～18岁同性别双生子337对,平均年龄(12.3±3.5)岁,其中同卵双生子257对,异卵双生子80对.采用DNA微卫星多态性鉴定卵性.应用Mx结构方程模型分别计算年龄和BMI调整前后瘦素的遗传度,并检验性别、年龄和BMI对于模型的作用.结果 不同性别间身高、体重和瘦素水平差异均有统计学意义(P值均＜0.05).相关分析显示,瘦素水平与性别、年龄和BMI相关(P值均＜0.0l).遗传分析发现,调整前年龄方差在女生中影响较大,而男生则受共同环境方差影响较大.调整后男生特异性性别方差降低,最适模型为ACE(scale)模型.男、女生瘦素遗传模型一致,遗传度为20％.结论 儿童青少年人群中瘦素水平与性别、年龄和BMI相关.瘦素受遗传和环境因素共同影响.调整年龄及BMI后,瘦素遗传度不受性别影响.     

Twin study of genetic and environmental effects on lipid levels

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.     

Alcohol effects on the percentage of beta waves in the electroencephalograms of twins

Electroencephalogram (EEG) recordings were made from 26 pairs of monozygotic (MZ) and 26 pairs of dizygotic (DZ) adult male twins, before and after alcohol ingestion. After a baseline EEG and a light breakfast, 1.2 ml/kg of ethanol was given orally over 15 min and the EEG repeated four times at hourly intervals. Alcohol caused a significant drop in the percentage of beta waves (14-30 cycles/sec) during the 1st hr. For the percentage of beta waves in 38 pairs of twins with complete data, MZ twin beta-wave intraclass correlations (RMZ) ranged between 0.85 and 0.91 before and after alcohol, but the DZ intraclass correlations (RDZ) started at 0.54 and fell to 0.05 at 2 hr after alcohol before recovering to baseline levels. These correlations resulted in heritability estimates [2(RMZ-RDZ)] of 0.68 at baseline and 1.73 at 2 hr. A heritability of 1.43 was found for the 1st hr drop in percentage of beta waves (RMZ = 0.78, RDZ = 0.06). These unrealistically high heritabilities, due to RDZ's approaching 0.0, suggest a failure of assumptions in the linear twin model that was used. Also, these findings are similar to, but more exaggerated than, findings in resting EEG's and visually evoked EEG potentials of twins and are compatible with the influence of gene interactions.     

Sex-specific effects for body mass index in the new Norwegian twin panel

Sex-specific effects for body mass index (BMI) were explored in a newly established, population-based Norwegian twin panel. The sample includes 5,864 individuals, aged 18–25 years, who responded to a questionnaire containing items for zygosity classification, height, weight, health, health-related behaviors, well-being, and demographic information. Among the 2,570 intact pairs who returned the questionnaire there were 416 identical (MZ) male pairs, 387 fraternal (DZ) male pairs, 528 MZ female pairs, 443 DZ female pairs, and 796 unlike-sexed pairs. Alternate sets of models testing for either sex-specific genetic or environmental parameters were evaluated using structural equation analysis. Results from the most parsimonious model indicated that the genes contributing to variation in BMI are not identical for men and women; rather, some genetic effects were shared by the sexes and some were unique to each sex. Total variation in BMI could be explained by sex-specific additive genetic effects, as well as genetic and non-shared environmental effects common to men and women. Estimates of heritability were .708 for men and .789 for women, and the male-female genetic correlation was 0.622. The series of models specifying sex-specific shared environment also fit the data and suggests that shared environmental factors may be important for males but not for females. The findings raise questions concerning the relationship between sex-specific effects for BMI and sex differences in health outcomes. ©1995 Wiley-Liss, Inc.     

双生子儿童贫血状况分析

目的通过分析双生子儿童贫血状况和贫血同病率,探讨其遗传和环境效应.方法选取5～19岁双生子228对,其中MZ(单卵双生子)142对,DZ(二卵双生子)86对,在DNA卵性鉴定基础上,以成对法计算同病一致率、调整BMI前后组内相关系数及遗传度.结果双生子儿童贫血检出率与一般人群无明显差异,贫血同病一致率分别为MZ 0.28,DZ 0.15,Hb(血红蛋白)遗传度为0.23.调整BMI前后MZ与DZ组内相关系数和遗传度无显著变化.结论儿童贫血状态受遗传及环境因素共同影响,环境效应更明显.     

Basal metabolic rate in monozygotic and dizygotic twins

The basal metabolic rate (BMR) was determined in 14 pairs of monozygotic (MZ; 11 females, 3 males) and 12 pairs of dizygotic (DZ; 10 females, 2 males) twins, with mean ages of 22.7 and 26 years. Zygosity was confirmed using DNA fingerprinting. When BMR was expressed as kJ/d, kJ/kg/d and kJ/kg FFM/d significant intra-class correlation coefficients were observed in the MZ twins of 0.82, 0.79 and 0.85, respectively. The DZ twins showed much lower intra-class correlations coefficients of 0.1, 0.07 and -0.04. Although the results of the study suggest a likely genetic component to the variation in BMR, they should be interpreted with caution as heritability estimates vary with the method of calculation. These will be critically discussed in the paper.     

恒牙列拥挤的双生子研究

目的 通过双生子研究遗传和环境因素对恒牙列拥挤形成所起的作用，以进一步研究恒牙列拥挤的影响因素。方法 以48对双生子作为研究对象，应用卵型鉴定技术分为单卵双生子组（MZ）和二卵双生子组（DZ），采取牙[牙合]石膏模型并进行测量，获取牙齿近远中径大小、牙弓弧长及牙列拥挤度等数据；采用Holzinger经典双生子法计算遗传度。结果 同卵与二卵双生于牙齿近远中径的平均值差别无统计学意义。说明牙齿近远中径在同卵．二卵双生子样本中平均水平接近。上下颌牙量遗传度较高。上颌为69．97％，下颌为75．73％；上颌牙弓弧长的遗传度（71．26％）明显高于下颌（31．33％）；单卵双生子和二卵双生子上下颌牙齿的拥挤度的对内相关系数较为接近，二卵双生子略低。遗传度很低，上颌为4．73％，下颌为10．3％。结论 上下颌牙量大小和上颌牙弓弧长受较强遗传控制。下颌牙弓弧长受弱遗传控制，恒牙列拥挤度遗传度很低，受环境因素影响较大。