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.     

3～6岁双生子体型遗传分析

目的分析3～6岁幼儿体型各因子的遗传度,探讨遗传与环境因素对其体型发育的影响。方法采用Heath-Carter体型法对72对3～6岁同性别双生子[同卵双生子(MZ)42对,异卵双生子(DZ)30对]的体型进行分析,用Holzinger公式估算体型各因子遗传度。结果二维空间的体型离散距离(SDD)和三维空间体型位置距离(SAD)显示,MZ的体型较DZ更为接近;体型各因子对间方差在2类双生子间均无明显差异,中因子和外因子的对内方差DZ均明显大于MZ、组内相关系数MZ均明显大于DZ;内、中、外3个因子的遗传度分别为0.38、0.67、0.73。结论遗传与环境因素对3～6岁幼儿体型发育均有一定影响,内因子主要受环境影响,中、外因子受遗传因素影响较大。     

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.     

Likelihood-based concordance tests for analysis of ascertained twin pair multinomial data

The classic twin model design has a wide application in human genetics. Under the assumption that nongenetic effects are shared to the same degree by monozygotic (MZ) and dizygotic (DZ) twin pairs, a test of the equality of casewise concordances between MZ and DZ twins provides a clue to the influence of genetic and environmental factors on a disease. The casewise concordance is the conditional probability that given that one member of a twin pair is affected, the other is also affected. When disease prevalence is low or cost-effectiveness is considered, collection of twin pairs by ascertainment for performing casewise concordance analysis is required. In this article, by defining an overall casewise concordance parameter, several likelihood-based tests, such as likelihood ratio test LR, score test Score, the usual Wald test Wald and an alternative Wald test WaldA are investigated for a test of the equality of concordances between ascertained MZ and DZ twin pairs under multinomial models. Simulation studies were conducted for data with small sample sizes. The results show that the type I error rates and power of LR and Score are stable only when the overall casewise concordances are not extremely small or large. The Wald has higher power performance in most cases but would slightly inflate type I error rates; the WaldA is the most robust and recommended approach.     

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.     

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.     

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。     

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)     

Concordance for mortality with special reference to ischaemic heart disease and cerebrovascular disease: A Study on the Swedish Twin Registry

The Swedish Twin Registry contains about 11 000 same-sexed twin pairs born between 1886 and 1925 with both members alive when the registry was formed in 1961. During the years 1962 to 1973, 2780 deaths occurred. 727 deaths were due to ischaemic heart disease (IHD), 345 due to cerebrovascular disease (CVD), and 727 due to cancer. The rate of concordance for the whole twin population revealed a significantly (p < 0.05) higher concordance rate for IHD among the male monozygotic (MZ) pairs as compared to the dizygotic (DZ) pairs (15.8% versus 8.0%). The corresponding figures for the female pairs were 11.0% (MZ) and 7.5% (DZ), respectively. With regard to death in CVD and cancer, the rates of concordance were about the same for MZ and DZ pairs in both males and females. When subgrouping was made for age groups, the difference in concordance rate for IHD in males was still more pronounced for the younger age group, born 1901–1925, (16.1% versus 5.4%). These data may indicate the existence of a genetic determination on death in IHD, especially in males, whereas a genetic determination on death in CVD and cancer seems more uncertain.     

Genetic and environmental influences on problematic masturbatory behavior in children: a study of same-sex twins

Child sexual behavior problems, such as excessive or public masturbation, are often judged to result from environmental stress or trauma. We studied the relative importance of genetic and environmental factors for problematic masturbatory behavior among nonreferred prepubertal children. All twins born in Sweden in 1985–86 were identified from the Swedish Twin Registry. Parents, mainly mothers, completed Child Behavior Checklist (CBCL) ratings (Achenbach, 1991) for 401 monozygotic (MZ) and 248 dizygotic (DZ) same-sex twin pairs (male–male or female–female) at age 7–9 years. Scores of two CBCL items concerning specific sexual behavior problems (Plays with own sex parts in public and Plays with own sex parts too much) were summed and the influence of genetic and environmental factors on variability assessed. The prevalence of problematic child masturbatory behavior was low and associated with other emotional and behavioral problems. The degree of problematic child masturbatory behavior resemblance was higher within MZ twin pairs as compared to DZ same-sex twin pairs. Model fitting indicated that genetic factors substantially influenced the studied behaviors (77%, 95% CI = 9–96%), although family environment also played a role. Our results suggest that hereditary factors should be considered together with stressful experiences such as sexual victimization in the evaluation of elementary school children presenting with problematic masturbatory behaviors. When interpreting the findings, the very brief measure of sexual problem behavior and low statistical power, precluding the analysis of possible coinheritance with other symptoms or disorders, should be borne in mind.     

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。     

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.     

Univariate genetic analyses of epilepsy and seizures in a population-based twin study: The Virginia twin registry

The purpose of this study was to examine the roles of genetic and environmental factors in the etiology of epilepsy and seizures in twins ascertained from the Virginia Twin Registry. Health history information on twins was collected by questionnaire. Concordance rates were calculated and used to estimate degree of concordance for seizure types in monozygotic (MZ) and dizygotic (DZ) twin pairs. Univariate twin analyses were performed for each epilepsy and seizure type to determine models which best explained observed variation. Health history information concerning epilepsy and febrile seizure occurrences was provided by members of 8,655 twin pairs; 6,684 of these supplied additional information reporting absence, complex partial, tonic-clonic, and unspecified seizures. Models including additive genetic and unique environmental factors best explained febrile seizures, epilepsy, complex partial seizures, and unspecified seizures. For complex partial seizures, however, the contributions of genetic and environmental effects did not vary across gender. These results show that, under univariate analysis methods, genetic factors played an important role in the expression of seizures in epilepsy, febrile seizures, unspecified seizures, and complex partial seizures. Additional support for these findings was provided by the concordance results for all categories except male twins reporting complex partial seizure occurrence. However, environmental influences still remained an important factor in seizure expression in these specific categories. Genet. Epidemiol. 15:33–49,1998. © 1998 Wiley-Liss, Inc.     

Concordance of ischemic heart disease in the NHLBI twin study after 14-18 years of follow-up

Morbidity and mortality were assessed in the NHLBI twin study at the end of 1987. Deaths were greater in DZ twins (58/520, 11.2%) than MZ twins (38/508, 7.5%). Ischemic heart disease concordances were 2.3 times higher in MZ pairs and 2.8 times higher in DZ pairs than expected based on the prevalence of ischemic heart disease in the cohort. Family history scores for heart disease, calculated 14-18 years earlier at entry to the study, were significantly higher in DZ pairs where one or both members later developed ischemic heart disease and in corcordant MZ pairs than in twin-pairs without any subsequent heart disease. Concordance rates were not significantly different between MZ and DZ pairs. The results agree with previous suggestions that selection at enlistment into the armed services over 40 years ago, as well as later volunteering for the NHLBI twin study, resulted in a decline in the number of concordant MZ pairs.     

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 and blood pressure levels in male twins in Utah

Healthy male monozygotic (MZ) and dizygotic (DZ) twin pairs (MZ pairs = 77; DZ pairs = 88) were studied to assess the effect of dietary intake, physical activity, physical fitness, body mass index (BMI), sum of the triceps and subscapular skinfold measurements, alcohol and caffeine consumption, and smoking patterns on blood pressure. Data on physical activity, detailed dietary intake, medical history, and demographics were obtained from a questionnaire. A bicycle ergometer was used to estimate level of fitness; other medical information was ascertained from physical examination. After normalizing the study variables, intraclass correlations for BMI and the sum of the triceps and subscapular skinfold measurements were higher in MZ than in DZ twin pairs (BMI: MZ r = 0.76, DZ r = 0.48; skinfolds: MZ r = 0.73, DZ r = 0.28), as were VO2max(MZ r = 0.63, DZ r = 0.25) and post-bike heart rate (MZ r = 0.69, DZ r = 0.19). Both systolic (SBP) and diastolic blood pressure (DBP) had high heritability estimates (SBP = 0.60, and DBP = 0.66). Using factor analysis, four major lifestyle factors were identified and categorized as: 1) dietary intake; 2) a factor heavily weighted by cigarette smoking, alcohol and caffeine consumption; 3) fatness; 4) physical activity and physical fitness. Adjustment for these factors did not alter heritability estimates for either SBP or DBP.     

Ambiguous relation between physical workload and low back pain: a twin control study

Aims: To examine the association between self reported physical workload and low back pain (LBP) in younger twins. To investigate whether genetic factors interact with physical workload in relation to LBP.

Methods: A twin control study was performed within a population based twin register using 1910 complete monozygotic (MZ) and same sexed dizygotic (DZ) twin pairs aged 25–42 and discordant for LBP. LBP in the affected twins was divided into two groups: "LBP for ≤30 days during the past year", and "LBP for >30 days during the past year". Physical workload was divided into four categories: "sitting", "sitting/walking", "light physical", and "heavy physical". Data were analysed in a matched design using conditional logistic regression. MZ and DZ twins were analysed separately and together in order to determine possible genetic influences in relation to physical workload and LBP.

Results: Statistically significant graded relations were found for increasing workload and LBP of longer duration but not for LBP of shorter duration (≤30 days during the past year). In both LBP groups the "sitting" and "sitting/walking" groups were not statistically different. MZ and DZ twins did not differ significantly with respect to LBP in the various workload groups.

Conclusions: There is evidence for a dose-response relation between physical workload and LBP of longer duration. Attention to clinically relevant subgroups based on duration, for example, is necessary in epidemiological studies dealing with LBP. Physical workload might be more important than genetic factors in LBP.

     

Physical activity,morbidity and mortality in twins: a 24-year prospective follow-up

The aim of this study was to find out whether persistent leisure-time physical activity, adjusted for genetic liability and childhood experiences, protect against occurrence of specific chronic diseases and all-cause mortality. Study design was a 24-year prospective follow-up after 6-year physical activity discordance in twin pairs. From 5,663 healthy adult twin pairs, 146 pairs (including 29 mozygotic) discordant for both intensity and volume of leisure physical activity at baseline in both 1975 and 1981 were systematically identified. Mortality and occurrence of chronic diseases (diabetes, hypertension, coronary heart disease defined according to reimbursable medication status) were followed for the period 1.1.1983–31.12.2006 for mortality and 1.1.1983–31.12.2004 for diseases. By end of follow-up, 19 inactive and 10 active co-twins had died. In the whole sample, HR of death adjusted for social class was 2.08 (95% CI 1.06–4.09) for inactive vs. active co-twins, the HR being 2.67 (95% CI 1.15–6.20) among DZ pairs with no mortality difference among the smaller number of discordant MZ pairs. The reimbursable medication analyses showed a tendency of higher risk for inactive vs. active co-twins. Among DZ pairs, HR of diabetes medication adjusted for social class was 2.73 (95% CI 0.62–12.00) and HR of hypertension medication was 2.14 (95% CI 0.94–4.89). This study supports the earlier findings that physical activity is associated with reduced mortality. However the difference was seen only in DZ pairs and therefore some residual genetic confounding effects on mortality cannot be excluded.     

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.