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

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

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.     

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.     

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.     

Birth weight and body composition in young women: a prospective twin study

BACKGROUND: The intrauterine environment may be critical for the development of obesity. Alternatively, the same genetic factors may influence both birth weight and adult body composition. OBJECTIVE: We evaluated the association between birth weight and adult body composition in female twins, which allowed us to control for maternal and genetic influences. DESIGN: Of 447 twin pairs randomly selected from the East Flanders Prospective Twin Survey, 238 pairs, aged 18-34 y, participated. Adult body mass, height, and lean body mass were measured, and the body mass index (BMI), waist-to-hip ratio, and sum of skinfold thicknesses were calculated. The twins were considered as individuals and pairs. RESULTS: When the twins were considered as individuals, twins who were heavier at birth were taller (3.3 cm/kg greater birth weight) and slightly heavier (1.13 kg/kg greater birth weight) as adults than were lighter twins. They also had more lean body mass and less subcutaneous and abdominal fat at birth. Pairwise comparison showed that for every level of intrapair birth weight difference (> or = 5%, > or = 10%, and > or = 15%), the twin who was heavier at birth was taller in adult life (0.8, 1.2, and 2.0 cm, respectively). When the intrapair birth weight difference exceeded 15%, the heavier twin was also heavier (3.1 +/- 6.08 kg) as an adult than her much lighter sister. CONCLUSION: Birth weight accounts for some of the differences in adult body composition between twins.     

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.     

双生子学龄儿童体格发育遗传学分析

目的 分析遗传与环境因素对学龄双生子儿童体格发育的影响,分析其中年龄和性别的作用.方法测量297对6～12岁(同卵167对,同性别异卵90对,异性别异卵40对)学龄儿童身高、坐高、体重、胸围、肱三头肌皮褶、肩胛下皮褶、髂前皮褶厚度;用Mx软件拟合最佳结构方程模型.结果各体格指标均与年龄相关,仅肱三头肌皮褶厚度与性别相关;各指标的遗传模型均为ACES,遗传方差组分高于环境方差组分,男性皮褶厚度的共同环境效应高于女性,皮褶厚度的年龄方差(0.02 ～0.17)明显低于其他指标(0.35 ～0.74);校正年龄后,遗传度分别为身高(男0.80,女0.83)、坐高(男0.76,女0.79)、体重(男0.53,女0.73)、胸围(男0.72,女0.66)、肱三头肌皮褶(男0.51,女0.87)、肩胛下皮褶(男0.56,女0.86)、髂前皮褶(男0.51,女0.83),女生体重及皮褶厚度的遗传度均明显高于男生.结论遗传因素对学龄儿童体格发育起主要作用,但年龄、性别对其也有一定影响.     

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.     

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.     

Birth weight and risk of angina pectoris: analysis in Swedish twins

Objective: Intrauterine nutrition approximated by birth weight has been shown to be inversely associated with risk of coronary heart disease (CHD). By investigating the association within twin pairs discordant for disease, the influence of genetic and early environmental factors is substantially reduced. Methods: We have investigated the association between birth weight and angina pectoris in same-sexed twins with known zygosity included in the population-based Swedish Twin Registry. Self-reports of birth weight and angina pectoris were collected in a telephone interview between 1998 and 2000. The cohort analyses were based on 4594 same-sexed twins, and the within-pair analyses included 55 dizygotic and 37 monozygotic twin pairs discordant for angina pectoris. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Results: Compared with birth weight between 2.0 and 2.9 kg, low birth weight (<2.0 kg) was associated with increased risk of angina pectoris in the twin cohort, (OR: 1.46; 95% CI: 1.14–1.87), but after adjustment for potential confounders the risk decreased, and did not reach significance. Within twin pairs discordant for angina pectoris, low birth weight was significantly associated with increased risk of angina pectoris within dizygotic twins (adjusted OR: 5.73; 95% CI: 1.59–20.67), but not within monozygotic twins (adjusted OR: 1.20; 95% CI: 0.40–3.58). Conclusions: The results suggest that genetic differences associated with foetal growth and adult risk of CHD may have affected previously reported associations between birth weight and CHD.     

Genetic and environmental influences on sleep problems: a study of preadolescent and adolescent twins

Background/Aim The aim of this study was to examine the extent to which additive genetic, shared environmental and non‐shared environmental factors contribute to adolescent and preadolescent sleep problems. Methods The sample consisted of a cohort of 270 monozygotic and 246 dizygotic twins from a university‐based twin registry. Results Results demonstrated that genetic and environmental influences each appear to be important to adolescent sleep problems. Conclusions While the magnitude of genetic influence on sleep problems was consistent with findings from the adult literature, it was smaller than in studies with younger children, suggesting genetic effects may be less influential in adolescence and adulthood.     

Genetic effects on weight change and food intake in Swedish adult twins

BACKGROUND: Obesity is influenced by genetic and environmental factors. Additionally, synergistic effects of genes and environments may be important in the development of obesity. OBJECTIVE: The aim of this study was to test for genetic effects on food consumption frequency, food preferences, and their interaction with subsequent weight gain. DESIGN: Complete data on the frequencies of consumption of 11 foods typical of the Swedish diet were available for 98 monozygotic and 176 dizygotic twin pairs aged 25-59 y who are part of the Swedish Twin Registry. The data were collected in 1973 as part of a questionnaire study. Body mass index was measured in 1973 and again in 1984. RESULTS: There was some evidence that genetic effects influenced the frequency of intake of some foods. Similarity among monozygotic twins exceeded that among dizygotic twins for intake of flour and grain products and fruit in men and women, intake of milk in men, and intake of vegetables and rice in women, suggesting that genes influence preferences for these foods. Analyses conducted for twins reared together and apart also suggested greater monozygotic than dizygotic correlations, but cross-twin, cross-trait correlations were all insignificant, suggesting that the genes that affect consumption frequencies are not responsible for mediating the relation between the frequency of intake and weight change. CONCLUSIONS: Genetic effects and the frequency of intake are independently related to change in body mass index. However, there was no suggestion of differential genetic effects on weight gain that were dependent on the consumption frequency of the foods studied.     

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.     

Genetic and environmental influences on body-fat measures among African-American twins

OBJECTIVE: To investigate the genetic and environmental influences on body-fat measures including waist circumference (WC), waist-to-hip ratio (WHR), and body mass index (BMI) among African-American men and women. RESEARCH METHODS AND PROCEDURES: Measurements were taken as part of the Carolina African American Twin Study of Aging. This sample currently comprises 146 same-sex African-American twins with an average age of 50 years (range, 22 to 88 years). This analysis included 26 monozygotic and 29 dizygotic men and 45 monozygotic and 46 dizygotic women. Maximum likelihood quantitative genetic analysis was used. RESULTS: In men, additive genetic effects accounted for 77% of the variance in WC, 59% in WHR, and 89% in BMI. In women, additive genetic effects accounted for 76% of the variance in WC, 56% in WHR, and 73% in BMI. The remaining variance in both men and women was attributed to unique environmental effects (WC, 21%; WHR, 36%; BMI, 11% in men and WC, 22%; WHR, 38%; BMI, 27% in women) and age (WC, 2%; WHR, 5% in men and WC, 2%; WHR, 6% in women). When BMI was controlled in the analysis of WC and WHR, it accounted for a portion of the genetic and environmental variance in WHR and over one-half of the genetic and environmental variance in WC. DISCUSSION: There are both genetic and environmental influences on WC, WHR, and BMI, and independent of BMI, there are genetic and environmental effects on WC and WHR among both genders. The results from this African-American twin sample are similar to findings among white twin samples.     

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.     

Familial patterns of covariation for cardiovascular risk factors in adults: The Victorian Family Heart Study

The Victorian Family Heart Study was established to address the causes of familial patterns in cardiovascular risk factors. From 1990 to 1996, a representative population sample of 783 adult families (2,959 individuals), each comprising both parents (40-70 years) and at least one natural adult offspring (18-30 years), was recruited in Melbourne, Australia. Included in both generations were 461 monozygotic and dizygotic twins as pairs or singletons. A multivariate normal model was used for pedigree analysis of height, weight, body mass index, diastolic and systolic blood pressure, pulse rate, and total and high density lipoprotein cholesterol. All traits showed evidence for additive genetic variation, explaining from 55% (height) to 26% (pulse) of age- and sex-adjusted variance. An effect persisting into adulthood of shared family environment during cohabitation explained from 39% (body mass index) to 13% (systolic blood pressure) of variance (not nominally significant for diastolic blood pressure). These shared environmental effects were strongest within twin pairs, less so for sibling pairs, and least for parent-offspring pairs (in which an effect was not observed for weight, diastolic and systolic blood pressure, and total cholesterol). On a background of genetic influences, there are periods in early life during which the family environment cements long-term correlations between adult relatives in cardiovascular risk factors.     

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.     

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.     

58对孤独症谱系障碍双胞胎临床特点及同病率分析

目的 分析58对孤独症谱系障碍(ASD)双胞胎临床特点及同病率,以及其遗传规律和影响因素。方法 收集1999-2015年就诊于中山大学附属第三医院发育行为中心的ASD双胞胎,对随访的58对ASD双胞胎临床资料进行总结分析,其中至少1名双胞胎诊断为ASD,通过统计描述,使用R软件进行分析同病率。结果 双胞胎出生体重较低,胎龄较小,围生期有较多高危因素;同卵双胞胎的同病率为73.68%,异卵双胞胎的同病率为12.82%,差异具有统计学意义(χ²＝18.81,P<0.001)。结论 ASD双胞胎同卵双胞胎具有较高的同病率,提示遗传因素是其重要病因。