Evidence of genetic susceptibility to infectious mononucleosis: a twin study

SUMMARY Infectious mononucleosis is a clinical manifestation of primary Epstein-Barr virus infection. It is unknown whether genetic factors contribute to risk. To assess heritability, we compared disease concordance in monozygotic to dizygotic twin pairs from the population-based California Twin Program and assessed the risk to initially unaffected co-twins. One member of 611 and both members of 58 twin pairs reported a history of infectious mononucleosis. Pairwise concordance in monozygotic and dizygotic pairs was respectively 12·1% [standard error (s.e.)=1·9%] and 6·1% (s.e.=1·2%). The relative risk (hazard ratio) of monozygotic compared to dizygotic unaffected co-twins of cases was 1·9 [95% confidence interval (CI) 1·1-3·4, P=0·03], over the follow-up period. When the analysis was restricted to same-sex twin pairs, that estimate was 2·5 (95% CI 1·2-5·3, P=0·02). The results are compatible with a heritable contribution to the risk of infectious mononucleosis.     

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.     

Effect of environmental and genetic factors on education-associated disparities in weight and weight gain: a study of Finnish adult twins

BACKGROUND: Disparities in body mass index (BMI) between persons with different educational levels in Western countries are well documented, but the background of these education-associated disparities remains poorly understood. OBJECTIVE: The objective was to examine the influence of environmental and genetic factors on education-associated disparities in self-reported BMI and weight change. DESIGN: Longitudinal postal surveys were performed in 1975, 1981, and 1990. The data were analyzed by using multivariate genetic models for twin data. The data derived from the Finnish Twin Cohort included 2482 monozygotic and 5113 dizygotic same-sex male and female twin pairs born between 1915 and 1957. RESULTS: Education-associated differences in BMI and in weight change were clear in 1975 and 1981, respectively, whereas no differences were seen in weight change between 1981 and 1990 when age and baseline BMI were adjusted for. The trait correlation between baseline BMI and educational attainment (-0.15 in men and women) was mainly due to correlations between additive genetic factors that contributed to BMI and education in men (-0.20; 95% CI: -0.25, -0.14) and women (-0.32; 95% CI: -0.40, -0.25) when adjusted for age. Among women, a weaker positive correlation was found for the unshared environmental effects contributing to the 2 traits (0.06; 95% CI: 0.02, 0.12). The same factors that affected the association between education and BMI in 1975 largely explained the association between education and weight change in 1981. CONCLUSION: The results suggest the possibility that common genetic factors affect educational attainment and body weight, which contribute to education-associated disparities in BMI in adulthood.     

The heritability of smoking behaviour in pregnancy, and the birth weights of offspring of smoking-discordant twins

Questionnaire information on smoking habits in pregnancy was collated in 341 monozygotic (MZ) and 321 dizygotic (DZ) female twin pair cases from a population-based Norwegian Twin Panel. In a multifactorial model, the intra-pair correlation in smoking was 0.797 (+/- 0.042) in monozygotic (MZ) and 0.443 (+/- 0.075) in dizygotic (DZ) twin pairs, indicating a substantial genetic influence on liability to smoke in pregnancy. The questionnaire information was linked with birth records in the Medical Birth Registry of Norway, and birth weights of offspring of 62 MZ and 100 DZ smoking-discordant twin pairs were studied. Offspring of smoking MZ twins weighed 127 g less than birth order matched offspring of the non-smoking co-twins. This finding is additional evidence that smoking is a direct cause of reduced birth weight in offspring.     

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)     

Future hospital care in a population-based series of twin pairs discordant for physical activity behavior

OBJECTIVES: This study investigated the association between physical activity behavior and morbidity, taking into account genetic selection. METHODS: Hospitalizations were followed from the beginning of 1977 to the end of 1986 in 710 same-sex healthy twin pairs discordant for leisure-time physical activity and in 151 pairs discordant for all physical activity at base-line in 1975. RESULTS: During the follow-up, among twin pairs discordant for leisure activity, the active member spent, on average, 43% fewer days in the hospital than the inactive member; the corresponding percentage was 55% among pairs discordant for all activity. CONCLUSIONS: Physically inactive behavior is associated with increased need for hospital treatments, even after genetic and other confounding factors are taken into account.     

Comparison of the Coincidence of Osteoporosis,Fracture, Arthritis Histories,and DEXA T-Score between Monozygotic and Dizygotic Twins: A Cross-Sectional Study Using KoGES HTS Data

We explored the genetic and environmental inter-relationships among osteoporosis, fracture, arthritis, and bone mineral density concordance in monozygotic twins compared to those in dizygotic twins. This cross-sectional research assessed data of 1032 monozygotic and 242 dizygotic twin pairs aged >20 years included in the Healthy Twin Study data of the Korean Genome and Epidemiology Study between 2005 and 2014. Outcomes of interest included illness concordance and absolute differences in dual-energy X-ray absorptiometry (DEXA) T-scores. We found comparable concordances of osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis between monozygotic and dizygotic twins. Medical histories of osteoporosis, fractures caused by accident or falling, osteoarthritis, and rheumatoid arthritis were not distinct between monozygotic and dizygotic twins. Accidental fracture occurrence in both monozygotic twins showed significantly lower odds than that in dizygotic twins. Genetic influence on liability to fracture risk might thus be maintained. DEXA T-scores for bone mineral density indicated more comparable tendencies within monozygotic twin pairs than within dizygotic ones, suggesting the relative importance of genetic contribution to bone mineral density. The relative importance of genetic factors in bone mineral density is sustained between monozygotic twins; overt disease expression of osteoporosis, fractures, or arthritis may be affected by environmental factors.     

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.     

Heritability estimate for refractive errors--a population-based sample of adult twins

The population-based Finnish Twin Cohort study was used to establish a heritability estimate for refractive errors especially for myopia. The twin cohort was derived from adult same-sexed twins in Finland. The total number of twins with both members alive in 1984 was 23,570. Of these, 3,676 twin pairs were monozygotic, and 8,109 pairs dizygotic. The sample for the present study was linked from the Finnish Police Force data base in 1984, where information of a person's possession of a driver's license and the obligation to wear glasses for far correction when driving a motor vehicle is recorded. Correlations in liability were estimated according to a multifactorial method of Smith. Falconer's heritability was 0.62 among males and 0.98 among females in the age group 28-29 years. When compared to previous twin studies of myopia, the proband concordance rates were higher for both MZ and DZ twin pairs.     

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.     

The Kaiser-Permanente women twins study data set

The Kaiser-Permanente Women Twins Study began with the establishment of a large registry of twins at Kaiser-Permanente, a managed health care program in Oakland, California. In 1978–79, 434 pairs of women twins, 255 monozygotic and 179 dizygotic, with average age 41 years, were recruited from this registry for a study of coronary heart disease risk factors. Previous analyses of these data have shown moderate heritability for blood pressure and high heritability for lipids, even after adjustment for differential environmental covariance between twin types. For GAW8, the data provided included age, race, weight, height, blood pressure, lipids, smoking, alcohol consumption, exercise, degree of contact between co-twins, menstrual status, and medication for hypertension. Exam 2 of this cohort was completed in 1989–90 and has recently reported nearly complete heritability for lipoprotein(a). © 1993 Wiley-Liss, Inc.     

Differences in birth weight and blood pressure at age 7 years among twins

Blood pressure later in life has been inversely associated with birth weight. However, concerns have been raised about whether this association merely reflects common environmental risk factors for both fetal growth restriction and high blood pressure or whether there is a genetic tendency to give birth to small babies and have high blood pressure. This study examined whether difference in birth weight of twins is associated with difference in blood pressure at age 7 years. The authors used data from the Collaborative Perinatal Project, United States, 1959-1966, which included 119 pairs of monozygotic and 86 pairs of same-sex dizygotic twins. The smaller twin in each pair had an average 300-g lower birth weight and was substantially thinner than the larger twin (p < 0.001). At age 7 years, body size and blood pressure were similar. Multiple linear regression was used to examine the association between difference in birth size and difference in blood pressure, adjusting for difference in body weight at age 7 years. None of the associations was statistically significant, and the direction of the associations was inconsistent. Further analyses stratified by birth weight, race, and sex revealed a similar, inconsistent pattern. The authors' findings fail to support the hypothesis that an unfavorable intrauterine environment adversely affects blood pressure in children.     

Association between height and coronary heart disease mortality: a prospective study of 35,000 twin pairs

An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.99 million person-years of follow-up. Cox and conditional logistic regression models were used. Per 1-standard deviation decrease in height, height was inversely associated with CHD mortality in men (hazard ratio = 1.08, 95% confidence interval (CI): 1.04, 1.12) and in women (hazard ratio = 1.06, 95% CI: 1.01, 1.10). A twin who had died from CHD was on average shorter than the co-twin within monozygotic pairs (odds ratio = 1.27, 95% CI: 1.12, 1.44, with no sex difference), whereas a weaker association was found within dizygotic pairs in men (odds ratio = 1.01, 95% CI: 0.91, 1.13) and in women (odds ratio = 1.14, 95% CI: 1.01, 1.28). The inverse association between height and CHD mortality found within monozygotic discordant twin pairs suggests that this association is because of environmental factors that directly affect height and CHD risk.     

Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute

The ankle-brachial index (ABI) is widely used in the clinical diagnosis of peripheral arterial disease. The contributions of genetic and environmental influences to normal and abnormal ABI values are unknown. In this study, the authors used available data on 94 monozygotic pairs and 90 dizygotic pairs of elderly, White, male twins examined in 1995-1997 to investigate the contributions of genetic and environmental influences to normative ABI values. Within-twin-pair correlations for normative ABI values were statistically significant, and the correlation in monozygotic twin pairs was significantly greater than that in dizygotic pairs. Structural equation modeling of the variance-covariance matrices of monozygotic and dizygotic twins indicated that 48% of the observed variability in ABI values could be attributed to additive genetic effects. In contrast, concordance rates for low ABI values (ABI< or =0.9) for both monozygotic and dizygotic twins were significantly greater than would be expected by chance alone, but within-pair monozygotic similarity was not significantly greater than dizygotic similarity. A matched-cotwin analysis in 21 pairs that were discordant for low ABI values found that twins with low ABI values were physically less active and more likely to be persistent smokers than their normal-control brothers. These findings reinforce the role of individual health practices (e.g., physical activity, smoking) in the manifestation of peripheral arterial disease among subjects matched for age, genetics, and early shared environment.     

成年双生子血尿酸遗传度研究

目的 用双生子研究方法 对成年人血尿酸的遗传度进行估计.方法 从青岛双生子库募集成年双生子.测量身高、体重和血尿酸.相同性别的双生子采用16个多态标记进行卵型鉴定.通过校正年龄、性别和BMI,来构建结构方程模型估计遗传度.结果 共收集687对双生子数据,其中同卵双生子420对,异卵双生子267对.经平方根转换后,男性血尿酸水平(17.47±1.91)略高于女性(15.22±1.70)(P＜0.0001),通过校正年龄、性别和BMI后双生子血尿酸的组内相关系数分别为,同卵双生子0.70、异卵双生子0.40.运用性别限制模型进行拟合,最佳模型AE模型,加性别遗传因素和特殊环境因素共同作用血尿酸的水平.血尿酸的遗传度为70.5%(95%CI:65.9～74.6),特殊环境因素占29.5%(95%CI:25.4～34.2).结论 遗传因素是影响样本双生子血尿酸水平的主要因素.     

Family environment, not heredity, accounts for family resemblances in food preferences and attitudes: a twin study

Monozygotic and same-sex dizygotic twin pairs reported on their food preferences, the variety of foods of the same general category (e.g. types of soup) in their diet, and their concern about contact of their food with disgusting or other unacceptable substances (contamination sensitivity). Although there was substantial resemblance between siblings for many of these items, there was no clear evidence for a heritable component on any item. The only case for which there was an interpretable and significantly greater resemblance among monozygotic than among dizygotic twins (out of 23 questions) was preferred degree of hotness resulting from chili pepper in foods. These results confirm the prediction that in omnivorous animals, such as humans, genetic predispositions will be minimal with respect to food. The modest sibling resemblances on a number of measures are primarily attributable to a shared environment.     

Stability and change of volume and intensity of physical activity as predictors of hypertension

AIMS: Controversy exists concerning intensity of physical activity and risk of hypertension. Also, the association between long-term changes in physical activity and hypertension is poorly known. Therefore we investigated how the stability and change of volume and intensity of physical activity are associated with the risk of hypertension in Finnish men and women. METHODS: A total of 3,931 men and 4,381 women responded to three questionnaires on health and lifestyle. Baseline data were gathered from two questionnaires, in 1975 and 1981. The subjects were 24-51 years of age, healthy, and non-hypertensive at baseline (1981). At the end of the follow-up, in 1990, the subjects responded to a third questionnaire, according to which we assessed the cumulative incidence of hypertension between 1982 and 1990. RESULTS: The cumulative incidence of hypertension from 1982 to 1990 was 10.2% in men and 8.0% in women. In men, the risk of hypertension was higher among those who were persistently not participating in vigorous physical activity (i.e. in both 1975 and 1981) (odds ratio, 1.60; 95% confidence interval, 1.15 to 2.24; p=0.006) than among those persistently participating, when all confounding factors were adjusted for. Among those participating in vigorous activity only in 1975 or in 1981 the risk was not significantly increased compared with those participating persistently. Volume of physical activity was not associated with hypertension. In women, there was no association between physical activity and incidence of hypertension. CONCLUSIONS: Compared with inactivity, persistent vigorous physical activity predicts a low risk of hypertension in men.     

Stress-Relaxation of Stretched Callus Strips

Among 706 male, dizygotic, smoking discordant twin pairs born in 1901 to 1925, 13 deaths occurred among nonsmokers or less exposed partners against 34 among smokers or more exposed. In 246 corresponding monozygotic pairs the figures were 14 against 9. The excess mortality among male dizygotic smokers was not associated with any specific cause of death. Four cases of lung cancer among males occurred only in smokers. Accidents and suicides seemed to be associated with smoking, supporting the hypotheses regarding differences in personality typebetween smokers and nonsmokers. Only time will show whether trends found are stable. The data suggest, however, that part of the greater mortality in smokers is not due to smoking per se but to factors associated with smoking.     

Environmental and behavioral determinants of fasting plasma glucose in women. A matched co-twin analysis

Comparing results of an unmatched analysis in a sample of unrelated persons created by randomly selecting one twin from each pair with results of a matched monozygotic co-twin analysis provides a means of distinguishing environmental influences from genetic influences on a dependent variable of interest. Determinants of the fasting plasma glucose level were investigated in a large sample of adult female nondiabetic twins from the Kaiser Permanente Twin Registry. In the subsample of unrelated persons, fasting plasma glucose was significantly and positively associated with age, body mass index, uric acid level, and alcohol intake and was significantly inversely related to leisure time physical activity. When monozygotic twins were treated as matched pairs, only the effects of body mass index and alcohol consumption remained significant, whereas the association with leisure time physical activity was greatly reduced and no longer statistically significant. These results suggest that behavioral and therefore alterable aspects of obesity and alcohol consumption influence the fasting plasma glucose level; alcohol consumption may be a risk factor for non-insulin-dependent diabetes mellitus; and common underlying genetic factor(s) may be responsible for the negative association between physical activity and fasting plasma glucose.     

中国成年双生子体质指数的分布特征

目的 描述中国双生子登记系统（CNTR）成年双生子BMI的分布特征,探索BMI在双生子人群中的特殊分布规律,为超重及肥胖高危因素分析和制定防制策略提供线索和基础资料。方法 选自CNTR中2010-2018年完成问卷调查的双生子对,纳入≥ 18岁具有完整双生子对登记信息,且身高、体重等关键变量无缺失或异常者进行分析,共计32 725对成年双生子。描述CNTR项目成年双生子BMI的人群、地区分布特征及双生子对内成员BMI差异的分布现况。结果 研究对象年龄（34.6±12.4）岁,同性别双生子对79.7%。研究对象平均BMI为22.5 kg/m²,超重率为23.7%,肥胖率为4.9%。男性、50~59岁组、北方地区、低文化程度者、在婚者的双生子超重率和肥胖率相对更高（P<0.001）。同卵和异卵间差异无统计学意义,但先出生的双生子超重和肥胖率略高于后出生者（P<0.05）。同性别双生子对内分析发现,对内BMI差异与年龄呈正相关（趋势性检验P<0.001）,异卵差异高于同卵,且卵型间差异随年龄增长发生变化。BMI一致率存在卵型差异（P<0.05）,同卵高于异卵。结论 本研究的双生子人群BMI的分布存在人群和地区差异;BMI为可遗传的性状,且遗传作用可能随年龄而变化。