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.     

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.     

Differences in Nutritional Intake,Total Body Fat,and BMI Score between Twins

The present study aimed to investigate the coincidence of obesity and nutritional intake in monozygotic twins compared to dizygotic twins. The data from the Korean Genome and Epidemiology Study (KoGES) from 2005 through 2014 were analyzed. Participants ≥ 20 years old were enrolled. The 1006 monozygotic twins and 238 dizygotic twins were analyzed for differences in self-reported nutritional intake, total body fat, and body mass index (BMI) using a linear regression model. The estimated values (EV) with 95% confidence intervals (95% CI) of the difference in dietary intake, total body fat, and BMI score were calculated. The monozygotic twin group and the dizygotic twin group showed similar differences in nutritional intake, DEXA fat, and BMI (all p > 0.05). The differences in nutritional intake of total calories and carbohydrates were lower in the monozygotic twin group than in the dizygotic twin group (all p < 0.05). The differences in total body fat were lower in monozygotic twins than in dizygotic twins (adjusted EV = 2427.86 g, 95% CI = 1777.19–3078.53 and adjusted EV = 1.90%, 95% CI = 1.33–2.46). Monozygotic twins had more similar dietary habits for total calories and carbohydrate intake. Other nutritional factors did not show differential similarity between monozygotic and dizygotic twins. Total body fat was more concordant in monozygotic twins.     

中国18岁以下双生子出生体重与超重/肥胖的关联分析

目的 分析出生体重与儿童时期超重/肥胖间的关联。方法 使用中国双生子登记系统基线调查的<18岁双生子人群(共8267对),采用双生子对内对照设计方法,探索出生体重与儿童青少年时期BMI及超重/肥胖之间的关联。结果 调整性别和卵型的影响后,出生体重每增加0.5 kg,超重/肥胖的风险:幼儿及学龄前期(≥ 2且<6岁)儿童增加0.87倍,学龄期(≥ 6且<12岁)儿童增加0.69倍,青春期(≥ 12且<18岁)青少年增加0.28倍。结论 双生子出生体重与幼儿及学龄期超重/肥胖存在正向关联,但在指导实施公共卫生干预措施时仍需谨慎。     

Perinatal characteristics and risk of polio among Swedish twins

Perng W, Cnattingius S, Iliadou A, Villamor E. Perinatal characteristics and risk of polio among Swedish twins. Paediatric and Perinatal Epidemiology 2012; 26: 218–225. Prenatal exposure to adverse environmental conditions is related to increased adult mortality in regions where infections are highly prevalent, yet there is little evidence of the impact of perinatal conditions on the risk of severe infections throughout life. Using prospectively collected data from 21 604 like‐sexed Swedish twins of known zygosity born in 1926–1958, we examined the risk of polio in relation to perinatal characteristics using cohort and nested co‐twin case–control analyses. Polio incidence was determined through an interview in 1998, and linkage with the Swedish national inpatient and death registries. There were 133 cases of polio. In the cohort analysis, birth length, birthweight and head circumference were positively associated with polio risk. After adjustment for sex, birth year, gestational age at birth and within‐twin pair correlations, twins of shortest length (<44 cm) had a 67% ([95% CI: 6%, 88%]; P = 0.04) lower risk of polio compared with the reference group (47–49 cm). After additional adjustment for birth length, every 100‐g increase in birthweight was related to a 34% increased risk of polio ([95% CI: ?1%, 82%]; P = 0.06), and every 10‐mm increase in head circumference was related to a 17% greater risk of polio ([95% CI: 5%, 31%]; P = 0.004). In co‐twin control analyses among 226 disease‐discordant twins, birth length, birthweight and head circumference were 0.3 cm (P = 0.19), 84 g (P = 0.07) and 3 mm (P = 0.08) higher in cases than controls, respectively. Similar associations were observed among monozygotic (n = 84) and dizygotic (n = 142) twins. These findings suggest that early intrauterine growth restriction may be inversely related to the incidence of polio.     

Low birthweight and Type 2 diabetes: a study on 11 162 Swedish twins

BACKGROUND: To investigate the association between low birthweight and diabetes in a population-based Swedish twin sample. Method A cohort of 11 162 same-sexed Swedish twins born between 1906 and 1958 was used in order to investigate the risk of developing Type 2 diabetes between and within twin pairs by utilizing random effects linear models. RESULTS: Between pairs there was a significant increase in risk of developing Type 2 diabetes for a 1-kg increase in their mean birthweight (odds ratio [OR] = 2.13; P < 0.01), adjusted for age, sex, body mass index (BMI), and smoking status. The corresponding risk within pair was 2.03 (P = 0.07) for monozygotic twins and 1.15 (P = 0.71) for dizygotic twins. The test of the heterogeneity of the within and between effects showed no significant difference between the estimates. CONCLUSIONS: The study suggests that reduced fetal growth increase the risk of Type 2 diabetes due to an in utero programming effect possibly caused by intrauterine malnutrition. However, it does not exclude the possibility of a common genetic mechanism.     

The role of genetic and environmental factors in the association between birthweight and blood pressure: evidence from meta-analysis of twin studies

BACKGROUND: An inverse association between birthweight and later blood pressure has been found in many studies in singletons. Twin studies have been used to examine whether genetic factors or family environment could account for this association. METHODS: A systematic review identified 10 studies covering 3901 twin pairs. Meta-analysis of regression coefficients for the association between birthweight and systolic blood pressure was carried out for unpaired versus paired associations and for paired associations in dizygotic versus monozygotic pairs. RESULTS: After adjustment for current weight or body mass index (BMI), the difference in systolic blood pressure per kg birthweight was -2.0 (95% CI: -3.2, -0.8) mmHg in the unpaired analysis and -0.4 (95% CI: -1.5, 0.7) mmHg in the paired analysis in the same subjects. In the paired analysis by zygosity, in all twins the coefficients were -0.7 (95% CI: -2.3, 0.8) mmHg in dizygotic pairs and -0.8 (95% CI: -2.1, 0.4) mmHg in monozygotic pairs, but in studies which included zygosity tests the coefficients were -1.0 (95% CI: -3.3, 1.6) mmHg in dizygotic pairs and -0.4 (95% CI: -1.9, 1.3) mmHg in monozygotic pairs. CONCLUSIONS: The attenuation of the regression coefficient in the paired analysis provides support for the possibility that factors shared by twins contribute to the association between birthweight and blood pressure in singletons. Comparison of paired analysis in monozygotic and dizygotic pairs could not provide conclusive evidence for a role for genetic as opposed to shared environmental factors.     

The influence of birth weight and genetic factors on lipid levels: a study in adult twins

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experience in utero growth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19-50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (-0.53 mmol/l per kg (95 % CI -0.97, -0.09), P = 0.02 and -0.39 mmol/l per kg (95 % CI -0.76, -0.02), P = 0.04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that the in utero growth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.     

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.     

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.     

No impact of surgery on cognitive function: a longitudinal study of middle-aged Danish twins

Purpose

To examine the association between exposure to surgery and 10-year change in cognitive functioning.

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.     

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.     

Effect of Interpregnancy Interval on Infant Low Birth Weight: A Retrospective Cohort Study Using the Michigan Maternally Linked Birth Database

Objective: To examine the relationship between interpregnancy interval and low birth weight (LBW), using the retrospective cohort design. Methods: We used the maternally linked Michigan livebirth data documented between 1989 and 2000 to evaluate LBW in relation to interpregnancy (i.e., delivery-to-conception) interval, overall and at levels of other reproductive risk factors. We fit separate logistic regression models for pairs of first-second, second-third, third-fourth, and fourth-fifth births to control for confounding. Results: Of the 565,911 infants identified, 5.5% had LBW. Univariate and stratified analyses showed that the risk for LBW was lowest when the interpregnancy interval was 18–23 months, and increased with shorter or longer intervals. This J-shaped relationship persisted after controlling for all risk factors simultaneously. For example, among the first-second birth pairs, the adjusted odds ratios (AORs) for LBW associated with interpregnancy intervals <6, 24–59, 60–95, and 96–136 months were 1.4 (95% confidence interval [CI] = 1.3–1.5), 1.5 (95% CI = 1.3–1.6), 1.1 (95% CI = 1.0–1.1) and 1.5 (95% CI = 1.3–1.8), respectively, compared with an interval of 18–23 months. Among the second-third birth pairs, the AORs were 1.5 (95% CI = 1.3–1.6), 1.3 (95% CI = 1.2–1.4), 1.1 (95% CI = 1.0–1.1), and 1.6 (95% CI = 1.3–2.0), respectively. Among the third-fourth birth pairs, the AORs were 1.2 (95% CI = 1.1–1.4), 1.3 (95% CI = 1.1–1.5), 1.0 (95% CI = 0.9–1.1), and 1.4 (95% CI = 1.0–2.0), respectively. Among the fourth-fifth birth pairs, the AORs were 1.3 (95% CI = 1.1–1.6), 1.2 (95% CI = 0.9–1.5), 1.1 (95% CI = 1.0–1.4), and 1.3 (95% CI = 0.8–2.3), respectively. The population attributable risk associated with interpregnancy intervals shorter than 18 months or longer than 23 months was 9.4%. Conclusion: These data suggest that spacing pregnancies appropriately could be used as a strategy for preventing LBW.     

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.     

Do genetic factors contribute to the association between birth weight and blood pressure?

OBJECTIVES: To evaluate whether genetic factors contribute to the association between low birth weight and increased blood pressure among adolescents. DESIGN: Historical cohort study of twin pairs. It was evaluated whether (1) a negative association between birth weight and systolic blood pressure was found in the overall twin sample and (2) whether the intrapair difference in birth weight correlated with the intrapair difference in systolic blood pressure-thereby controlling for the effect of genetic factors (all in monozygotic and on average half in dizygotic pairs). SETTING: The Minnesota Twin Family Study. PARTICIPANTS: 1311 pairs of adolescent twins. MAIN RESULTS: A negative association between birth weight and systolic blood pressure was retrieved in the overall sample. The regression coefficient after controlling for current weight was -1.88 mm Hg/kg (SE 0.61), which corresponds to results from previous studies of singleton adolescents. The regression coefficient fell to -0.64 mm Hg/kg (SE 0.86) when the intrapair analyses were used. The largest reduction was observed among monozygotic twins: from -2.44 mm Hg/kg (SE 0.75) in the overall monozygotic twin sample to -1.06 mm Hg/kg (SE 1.14) in the analyses of the within monozygotic pair differences. CONCLUSION: The association between low birth weight and increased blood pressure later in life is well established. "The fetal programming hypothesis" suggests that the association is caused by intrauterine malnutrition while a new hypothesis "the fetal insulin hypothesis" proposes that genetically determined insulin resistance also contributes significantly to the association. A recent twin study of middle aged twins showed no evidence for an influence of genetic factors while this larger study provides support for the fetal insulin hypothesis: the association between birth weight and blood pressure attenuated among adolescents when genetic factors were controlled. Together this suggests an important contribution of genetic factors to the association between fetal growth and systolic blood pressure in adolescence.     

Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005–2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.     

A Discordant Monozygotic Twin Approach to Testing Environmental Influences on Sexual Dysfunction in Women

The present study explored the causal role played by putative environmental factors on variation in female sexual dysfunction (FSD) by investigating FSD discordant monozygotic (MZ) twins, which permits a control over genetic confounders. In a population-based sample of female twins aged 25–69 years (M = 55 years), MZ twins discordant for recent and lifelong FSD were selected. Sample sizes varied depending on the specific sexual problem (N = 33–90 pairs). The Female Sexual Function Index (FSFI) score was used to discriminate cases from controls. Once genetic factors were controlled for, relationship satisfaction emerged as the strongest independent predictor for recent and lifelong FSD, being associated with FSFI dimensions measuring desire, arousal, and lubrication problems. The association with orgasm problems was especially strong (OR 7.1, 95 % CI: 1.9–25.3) as was the association with sexual dissatisfaction (OR 5.1, 95 % CI: 2.1–12.1). Furthermore, obsessive–compulsive symptomatology was weakly associated with desire problems (OR 1.5, 95 % CI: 1.4–1.8) and anxiety-sensitivity with orgasm problems (OR 1.1, 95 % CI: 0.9–1.3). Negligible effects were found for personality factors and small effects for self-reported abusive experiences. These data indicate, for the first time, that in women at identical genetic risk, relationship factors play a key role in the development of sexual problems. These findings require replication in prospective designs which can provide additional powerful tests of the direction of causality between interpersonal factors and later sexual dysfunction.     

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.     

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.