The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results

Coronary heart disease (CHD) risk factors were studied in 250 monozygotic (MZ) and 264 dizygotic (DZ) male veteran twin pairs, aged 42-56. All coronary heart disease risk factors studied showed significant correlations in both MZ and DZ twins. Substantial genetic variation was detected for height, blood pressure, glucose intolerance, uric acid, plasma triglyceride, and relative weight but little or no significant genetic variability in low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), total plasma cholesterol or hematocrit was demonstrable. These findings suggest that familial aggregation results from genetic influence on blood pressure, glucose intolerance, uric acid, triglyceride and, possibly, obesity, while largely shared environmental factors contribute to familial similarities in HDL, LDL, total cholesterol and hematocrit.     

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.     

The impact of genes and pre- and postnatal environment on the metabolic syndrome. Evidence from twin studies

Our population-based Danish twin study demonstrated a genetic influence on several of the components included in the metabolic syndrome, i.e. glucose intolerance, overall obesity, systolic and diastolic blood pressure and low levels of HDL-cholesterol. Abdominal obesity, insulin resistance and hypertriglyceridaemia had, on the other hand, a relatively higher environmental aetiological component. Furthermore we demonstrated a difference in aetiology among male and female twins indicating an influence of sex on several of the components in the metabolic syndrome. Studies have demonstrated an impact of the intrauterine environment (i.e. low birth weight) for the development of the components in the metabolic syndrome. The validity of conclusions drawn from classical twin studies has therefore been questioned due to the different prenatal circumstances characterising monozygotic (MZ) and dizygotic (DZ) pregnancies. Due to a potentially more adverse intrauterine environment among MZ compared to DZ twins, MZ twins may be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profiles after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--together with higher levels of total-cholesterol and triglycerides among MZ compared to DZ twins demonstrate an effect of zygosity (i.e. intrauterine environment) on these metabolic variables and therefore question the assumption of equal pre- and postnatal environment in MZ and DZ twins. Our studies provide further evidence for a prenatal component in the aetiology of the components included in the syndrome and question the validity of classical twin studies on phenotypes with a known prenatal aetiological component. However, our present knowledge is currently far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of the metabolic and haemodynamic components included in the metabolic syndrome.     

双生子A型人格与高血压及血生化指标研究

目的 了解双生子A型人格与高血压及血液生化指标的关系。方法 利用遗传流行病学方法对青岛市89对24岁以上双生子(同卵55对，异卵34对)进行调查。并进行A型人格测试，以比较同卵与异卵双生于A型人格得分的相关程度、A型人格及血压的一致性。推测遗传与环境因素对A型人格的影响，A型人格与高血压的关系，并探讨血液生化指标与A型人格的关系。结果 经KAPPA一致性检验，同卵(MZ)双生子之间A型人格存在着显的一致性(P＜0．001)，而异卵(DZ)双生子之间的一致性无显性差异(P＝0．802)。同时，MZ双生子之间A型人格和血压也存在显的一致性(P＜0．001)，而DZ双生子之间A型人格和血压无明显一致性(P＝0．102)。有A型人格的双生子血压的收缩压明显高于非A型人格的双生子(P＜0．05)。许多生化指标与A型人格因素相关，但是所计算出的相关系数大都小于0．30，属于弱相关。结论 MZ双生子A型人格及高血压之间存在着显的一致性，而这种一致性在DZ双生子表现不明显。A型人格是高血压的危险因素之一。A型人格与所研究血液基本生化指标之间相关较弱。     

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.     

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.     

Twins, smoking and mortality: a 12-year prospective study of smoking-discordant twin pairs

Despite the increasing scientific evidence for a causal role of tobacco smoking in lung cancer and coronary heart disease, critics, several decades ago, put forward an alternative hypothesis. The constitutional hypothesis has stated that there are genetic or other common factors, which predispose both to smoking and disease, but that the two are not causally related. A critical test of this hypothesis is the study of disease in monozygotic (MZ) twin pairs in which one smokes and the other never has. Earlier twin studies found only small differences in the mortality of smoking and nonsmoking twins of discordant pairs. In the Finnish Twin Cohort, a population-based panel of adult like-sexed twin pairs, a questionnaire study carried in 1975 permitted identification of twin pairs discordant for cigarette smoking. The nonsmoking cotwins had never been regular smokers. The smoking twins were divided into 1278 current smokers [CS; 143 MZ and 598 dizygotic (DZ) males and 171 MZ and 585 DZ females] and 1210 former smokers (FS; 129 MZ and 408 DZ males and 113 MZ and 341 DZ females). Exposure to tobacco was much higher among males; over 25% of men smoked 20 or more cigarettes daily compared to less than 10% of women. Follow-up of mortality yielded data on time and cause of death. Analyzing on first deaths from concordant pairs, there were 13 deaths in the smokers of male CS MZ pairs and 1 death in the nonsmoking cotwins (relative risk = 13.0, P less than 0.01). Excess mortality was also found for male CS DZ smokers (RR = 2.43, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Modest associations between self-reported physical workload and neck trouble: a population-based twin control study

Objectives

To investigate the relationship between self-reported physical workload and neck trouble (NT) in twins. Additionally, to explore whether the relationship between physical workload and NT is influenced by genetic factors.

Methods

A twin control study was performed within a population-based, cross-sectional questionnaire study using 3,208 monozygotic (MZ) and same-sexed dizygotic (DZ) twins aged 19–70. Twin pairs discordant for self-reported NT during the past year (“Any NT”) were included. Self-reported physical workload in four categories was used as exposure (“sitting,” “sitting and walking,” “light physical,” and “heavy physical” work). Paired analyses including conditional logistic regression were made for all participants and for each sex, and MZ and DZ pairs separately.

Results

No marked associations between physical workload and NT were seen. A moderate risk elevation in “heavy physical” work was seen in DZ men (odds ratio 2.3, 95 % confidence intervals 1.3–4.0), but not in MZ men or the MZ or DZ women.

Conclusions

The findings in some degree supported that “heavy physical” work is a determinant of NT, perhaps only in men, but hardly of any greater importance. The different results between DZ and MZ men suggest that genetic factors influence the relationship between physical workload and NT.     

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.     

遗传与环境因素对女性青春期性征发育的影响

目的探讨遗传与环境因素对女性青春期性征发育的影响,为进一步深入研究女性青春期发育提供依据。方法以学校登记为基础,募集6~18岁女性双生子180对,其中单卵双生(MZ)132对,二卵双生(DZ)48对,按Tanner标准进行青春发育分期,询问有无月经初潮及月经初潮年龄。结果乳房开始发育的年龄为9~12岁,阴毛开始发育的年龄集中在9~13岁,月经初潮年龄多集中在11~13岁。月经初潮、性征发育一致率均为MZ>DZ,月经初潮的遗传指数为0.71,乳房和阴毛发育的遗传指数分别为0.34,0.45。月经初潮年龄的组内相关系数MZ>DZ(P<0.001),偶内均方MZ相似文献   

Heritability of body size and muscle strength in young adulthood: a study of one million Swedish men

Moderate heritability for skeletal muscle strength has been reported in twin studies, but genetic co-variation between muscle strength at different parts of body and body size is not well known. Further, representativeness of twin cohorts needs to be critically evaluated. Height, weight, elbow flexion, hand grip and knee extension strength were measured in young adulthood in 1,139,963 Swedish men born between 1951 and 1976. We identified 154,970 full-brother pairs and 1582 monozygotic (MZ) and 1864 same-sex dizygotic (DZ) complete twin pairs. The data were analyzed using quantitative genetic modeling for twin and family data. Twins compared to singletons and MZ twins compared to DZ twins were shorter, lighter and had lower muscle strength. In singletons, there was more variation in weight and the strength measures compared to twins with known zygosity but not when compared to twins with unknown zygosity. Full-sib correlations for these traits were lower than DZ correlations. Additive genetic factors explained 81% of variation in height, 59% in body mass index and 50-60% in the strength measures. Additive genetic correlations varied from 0.13 between height and elbow flexion strength to 0.78 between elbow flexion and hand grip strength. Our results suggest that extra variation may exist in general populations not found in twin samples, probably because of selection due to non-participation. This may have inflated heritability estimates in previous twin studies. Nonetheless, we showed that genetic factors affect muscle strength and part of these genes are common to different strength indicators and body size.     

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%.     

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.     

Genetic and Environmental Influences on 2D:4D Finger Length Ratios: A Study of Monozygotic and Dizygotic Male and Female Twins

Recent studies have shown significant sex differences in the pattern of 2D:4D finger length ratios in humans and several other mammalian species. In humans, these ratios are suggested to be negatively correlated with prenatal exposure to testosterone, positively correlated with prenatal estrogen, and exhibit sex specific patterns of association with sexually dimorphic clinical phenotypes. However, the relative contributions of genetic and environmental influences on digit ratios in men and women are currently unknown. Therefore, the purpose of the current study was to examine genetic and environmental influences on 2D:4D ratios in twins. Participants included 146 monozygotic (MZ) and 154 dizygotic (DZ) adult male and female twins participating in the Michigan State University Twin Study of Behavioral Adjustment and Development. Overall, biometric model-fitting analyses indicated significant additive genetic and nonshared environmental influences on digit ratios. Findings suggest greater similarity between 2D:4D ratios in MZ relative to DZ twins that can be accounted for by genetic and nonshared environmental factors.     

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。     

Genetic susceptibility to burnout in a Swedish twin cohort

Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959–1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same—and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout.     

Genetic and developmental influences on susceptibility to epilepsy: evidence from twins

This study evaluated genetic and developmental contributions to epilepsy, using data on epilepsy and multiple births in the sibships of 1981 probands with epilepsy. Prevalence of a history of epilepsy was much higher in monozygotic (MZ) than in dizygotic (DZ) co-twins of probands (35.0% vs. 3.7%), but prevalence was not significantly higher in DZ co-twins than in singleton siblings. The proportion of individuals who were MZ twins was higher among probands with epilepsy than among their non-co-twin siblings without epilepsy (odds ratio 2.5, 95% CI 1.31-4.85). However, the proportion who were DZ twins was similar among probands and unaffected siblings (odds ratio 1.0, 95% CI 0.67-1.60). These findings suggest that the increased prevalence of epilepsy in MZ co-twins of probands may be partly explained by developmental factors related to MZ twinning, rather than by their genetic identity with the probands.     

LISREL modeling of high density lipoprotein cholesterol (HDL) levels in male twins

Based on the LISREL modeling approach for data from monozygotic (MZ) and dizygotic (DZ) twins [Heath et al., 1989; Neale and Cardon, 1992], the hypothesized variance of the logarithm of high density lipoprotein cholesterol due to additive genetic factors was estimated to equal 19% for males. Unobserved common environment accounted for 32% of the variance of log HDL. Both estimates controlled for body mass, alcohol consumption, and smoking. The model had very strong goodness-of-fit indices. © 1993 Wiley-Liss, Inc.     

Smoking and mortality: a 21-year follow-up based on the Swedish Twin Registry

Data on smoking and mortality from the Swedish Twin Registry were analysed as a prospective cohort study and as a co-twin control study. The twin method involves control of genetic and early environmental factors and thereby a general control of the nested factors that may act as confounders, adjustments not obtainable in ordinary study designs. In the cohort analyses the following relative risks for cigarette smokers were found for men and women, respectively: death all causes 1.4 (90% Cl 1.3; 1.5), 1.4 (1.3; 1.5), CHD death 1.4 (1.3; 1.7), 1.6 (1.3; 2.0), lung cancer 19.7 (9.1; 42.7), 5.1 (3.0; 8.7), and other cancers 1.2 (1.0; 1.4), 1.2 (1.0-1.4). The comparison of deaths in cigarette-smoking twins and their non-smoking co-twins gave the following risk estimates for monozygotic (MZ) men: death all causes 1.6 (35 versus 22 first deaths), CHD death 2.8 (11 versus 4). The results for dizygotic (DZ) males and for females were in agreement. Four lung-cancer deaths occurred in MZ and 17 in DZ smoker twins while the non-smoker co-twins showed two such cases (DZ women). Other cancer deaths did not occur more often in the smoker than in the non-smoker twin. The impact of smoking on mortality, CHD death and lung cancer is also valid among smoking discordant twins.