Twin study of genetic and environmental effects on lipid levels

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.     

The association between body height and coronary heart disease among Finnish twins and singletons

OBJECTIVE: An inverse association between body height and the incidence of coronary heart disease (CHD) has been observed. However, the mechanisms behind this association are still largely unknown. We will examine the role of genetic and familial factors behind the association in a large twin data set. DESIGN AND SETTING: The data were derived from the Finnish Twin cohort including 2438 singletons, 4073 monozygotic (MZ) twins, and 9202 dizygotic (DZ) twins aged 25-69 years at baseline in 1976. Incident CHD cases were derived from hospital discharge data and cause of death data between 1977 and 1995. Cox regression analysis and conditional logistic regression analysis were used. RESULTS: In population-level analyses no differences in the general risk of CHD between zygosity groups were found. The association between body height and CHD was similar between sexes and zygosity groups. When men and women in all zygosity groups were studied together an increased risk of CHD was found only among the shortest quartile (hazard ratio [HR] = 1.34, 95% CI: 1.14-1.57). Among the twin pairs discordant for CHD a suggestive increased risk for the shorter twin was seen among DZ twins (odds ratio [OR] = 1.19, 95% CI: 0.95-1.48) when men and women were studied together. CONCLUSION: An inverse association between body height and CHD was broadly similar between sexes and twin zygosity groups and was associated with short stature. Among discordant twin pairs we found a weak association among DZ twins but not MZ twins. This may suggest the role of genetic liability behind the association between body height and CHD.     

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

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

青岛市成人双生子血脂相关指标的遗传度研究

目的了解成人双生子血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)的水平及其遗传度。方法选择青岛市双生子库中316对18到60岁的健康成人双生子,用自动生化分析仪检测其空腹血清TC、HDL-C、LDL-C、TG的浓度。鉴定卵性后,用Mx软件拟合遗传模型,调整性别、年龄后,计算血脂相关指标的遗传度。结果双生子空腹血清TC、HDL-C、LDL-C、TG水平的均值分别为(4.52±1.08)、(1.46±0.39)、(2.58±0.79)、(1.11±0.77)mmol/L。Mx软件拟合结构方程模型结果显示,TC、HDL-C和LDL-C三项指标的最适模型为AE模型,其遗传度依次为53%、62%和57%。TG的最适模型为CE模型,遗传度为0。结论遗传因素和环境因素对TC、HDL-C和LDL-C的浓度都有重要影响,而TG主要受到环境因素的影响。     

双胎儿童孤独症谱系障碍广义遗传度与临床评估结果的影响因素研究

目的分析36对双胎儿童的孤独症谱系障碍(ASD)的同患率、广义遗传度,建立双胎回归模型,探讨随访资料中临床评估结果的影响因素。方法收集2016-2018年就诊于复旦大学附属儿科医院的部分双胎儿童,纳入标准:双胎至少一胎为ASD患儿,或双胎均为正常发育(NT)儿童,收集儿童的一般情况,采用孤独症诊断观察量表(ADOS)和Griffiths精神发育量表(GMDS)对儿童的社交能力和总发育商进行评估,使用R统计建模语言和双胎分析软件包mets建立模型。结果在36对双胎中,同卵双胎ASD共患率为66.7%,异卵双胎ASD共患率则为16.7%;ASD风险因素的最佳拟合为包含性别和体重的AE模型,广义遗传度接近90.4%(95%CI:65.2%~115.7%),但临床协变量和遗传因素对ASD预测的作用均不显著;孤独症诊断观察量表中重复和刻板行为(ADOS-RRB)的最优模型为加入自闭症诊断、体重、受孕方式与患儿年龄在内的AE遗传模型,孤独症诊断观察量表中社交情感(ADOS-SA)的最优拟合模型为引入性别、患儿年龄、母亲教育程度与受孕方式在内的CE遗传模型,Griffiths精神发育量表中总发育商(GMDS-DQ)的最优模型为ASD诊断、是否早产、性别在内的CE遗传模型,非共享环境因素对ADOS-RRB(P=0.000 2)、ADOS-SA(P<0.000 1)以及GMDS-DQ(P<0.000 1)的影响差异均有统计学意义。结论遗传因素是ASD发生的重要因素,非共享环境因素与ASD临床评估结果具有一定相关性。     

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.     

Male factor infertility: a twin study

There is a considerable body of literature on the causes of female infertility, but far less is known about male factor infertility. We conducted a classical twin study to estimate the genetic influence on 12-month male factor infertility. The study used the Vietnam Era Twin (VET) Registry, which includes male twin pairs born between 1939 and 1957, and who served in the US military between 1965 and 1975. In 1987, a health survey was mailed to all twins and obtained a 74% response rate. The current analyses comprised 1795 complete pairs in which both twins were married only once. Proband-wise concordance rates, tetrachoric correlations, and a bivariate probit model were used to calculate estimates of familial clustering and heritability for male factor infertility. The proband concordance rate for male factor infertility was 38% [95% CI 32.8, 42.4] in monozygotic (MZ) pairs and 33% [95% CI 28.0, 38.6] in dizygotic (DZ) pairs. The tetrachoric correlations for male infertility were 0.15 in MZ and 0.04 in DZ pairs. This pattern provides evidence of familial clustering, although genetic influence was not evident (P = 0.21). The current study identified that 12-month male factor infertility clustered within families. However, results suggest that factors unique to individual twins may play a more prominent role in male infertility than additive genetic effects or the common environment.     

A genetic and environmental analysis of a twin family study of alcohol use,anxiety, and depression

Alcohol consumption, anxiety, and depression were measured by questionnaire in 572 twin families ascertained from the Institute of Psychiatry (London) normal twin register, each family consisting of an adult twin pair, their parents, and siblings-a total of 1,742 individuals. A multivariate normal model for pedigree analysis was applied to each variable, with power transformations fitted to maximise the fit with distributional assumptions. The effect of shared twin environment was estimated by considering the measured cohabitation history of twin pairs. For log-transformed alcohol consumption, amongst current drinkers this effect was the same for MZ and DZ pairs but depended on the cohabitation status of pairs. For both anxiety and depression the effect was clearly not the same for MZ and DZ pairs. Therefore the basic assumption of the classical twin method appears to be invalid for all three traits. Estimates of heritability derived from these analyses were compared with those obtained (1) by applying the classical twin method to twin data only, and (2) by a pedigree analysis ignoring the effect of shared twin environment. For all variables there were considerable differences between estimates based on the three models. This study illustrates that data from twins and their relatives which includes information on cohabitation history might distinguish shared genes and shared environment as causes of familial aggregation. In these behavioral traits the effect of shared twin environment may depend on zygosity and play a major role in explaining familial aggregation in twin family data.     

Migration and coronary heart disease: A study of Finnish twins living in Sweden and their co-twins residing in Finland

BACKGROUND: Finland and Sweden are neighbouring countries with a substantially higher incidence and mortality from coronary heart disease (CHD) in Finland. Migration from Finland to Sweden has resulted in a population of about 187,000 Finnish immigrants, with a higher risk of CHD than Swedes. The aim of the present study was to analyse the prevalence of CHD in migrants to Sweden compared with co-twins remaining in Finland. METHODS: The study population consisted of twin pairs of the Finnish Twin Cohort Study where at least one twin had lived one year or more in Sweden, including 1,534 subjects and 251 complete twin pairs discordant regarding residency in Sweden. Emigrant twins were compared with nonmigrant co-twins regarding prevalence of CHD in 1998. CHD prevalence was assessed by self-reported questionnaires validated using information from a clinical examination. RESULTS: Self-reported CHD showed a good correspondence with clinical diagnosis. Differences in social and behavioural risk factors for CHD among men were small but emigrants were more physically active than non-migrants. Female emigrants had less overweight and better education, but were more often working class than non-migrants. Intra-pair comparisons restricted to migration discordant pairs showed a tendency towards a reduced prevalence of CHD in the migrant co-twins (0.6; 0.3-1.4). In analyses of all subjects disregarding pair status, emigrants showed a reduced prevalence of CHD compared with subjects always living in Finland (0.6; 0.4-0.9). CONCLUSION: Emigration from Finland to Sweden may be associated with a reduced prevalence of CHD. The causes are most likely multifactorial and may involve changes in dietary habits, physical activity, psychosocial factors, and inflammation.     

儿童青少年双生子瘦素遗传度估计及影响因素分析

目的 分析影响儿童青少年瘦素的遗传因素和环境因素,探讨性别、年龄和体质量指数(BMI)的作用,为儿童肥胖早期预防提供依据.方法 选择6～18岁同性别双生子337对,平均年龄(12.3±3.5)岁,其中同卵双生子257对,异卵双生子80对.采用DNA微卫星多态性鉴定卵性.应用Mx结构方程模型分别计算年龄和BMI调整前后瘦素的遗传度,并检验性别、年龄和BMI对于模型的作用.结果 不同性别间身高、体重和瘦素水平差异均有统计学意义(P值均＜0.05).相关分析显示,瘦素水平与性别、年龄和BMI相关(P值均＜0.0l).遗传分析发现,调整前年龄方差在女生中影响较大,而男生则受共同环境方差影响较大.调整后男生特异性性别方差降低,最适模型为ACE(scale)模型.男、女生瘦素遗传模型一致,遗传度为20％.结论 儿童青少年人群中瘦素水平与性别、年龄和BMI相关.瘦素受遗传和环境因素共同影响.调整年龄及BMI后,瘦素遗传度不受性别影响.     

Genetic Contribution to Suicidal Behaviors and Associated Risk Factors among Adolescents in the U.S.

This paper examines genetic contribution to suicidal behaviors and other risk factors associated with suicidal behavior among adolescents in the U.S. Using adolescent twin data in the National Longitudinal Study of Adolescent Health (N=1448), we compared concordance in suicidal ideation and attempt among monozygotic (MZ) and dizygotic (DZ) twins. Heritability of risk factors for suicidal behaviors also was examined using Pearson correlation and mixed-model analyses. A trend of higher concordance in suicidal ideation and attempt was found among MZ than DZ twins but the difference was not statistically significant by the stringent test of bootstrapping analysis. Evidence of heritability was found for several suicide risk factors. The percentage of variance explained by heritability was larger among female twins for depression, aggression, and quantity of cigarettes smoked in comparison to heritability estimates for male twins. However, estimated heritability was larger among male than female twins for alcohol use and binge drinking. Heritability influence was negligible among both sexes for other drug use. Risk factors for suicidal behaviors among adolescents may be heritable. Gender differences found in the heritability of some suicide risk factors suggest these genetic contributions are gender specific. Future research examining potential interactions between expression of genetic influence and particular environmental contexts may enhance prevention and intervention efforts.     

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.     

Selective international migration by social position, health behaviour and personality

BACKGROUND: Immigrants is an important minority in many countries, but little is known how they are self-selected. We analysed differences in psycho-social and health behavioural factors between international migrants and non-migrants prior to migration in a large cohort of Finnish twins. METHODS: A questionnaire was sent to Finnish twins in 1975 (response rate 89%, N = 26555 twin individuals). Follow-up data on migration and mortality were derived from population registries in Finland and Sweden up to 31 March 2002. In 1998, another questionnaire was sent to Finnish twins migrated to Sweden and their co-twins (response rate 71%, N = 1534 twin individuals). The data were analysed using Cox and conditional logistic regression models. RESULTS: Life dissatisfaction, higher alcohol use and smoking at baseline predicted future migration. In men additionally, unemployment, neuroticism and extroversion increased the probability to migrate. Similar associations were found for alcohol use in men and smoking in men and women within twin pairs discordant for migration. Twins also reported retrospectively that prior to migration the migrated twin had been less satisfied with his/her educational institution or job and was generally less satisfied with life, used more alcohol (men) and smoked more (women) than the co-twin stayed in Finland. CONCLUSION: Migrants are self-selected by health behavioural and personality factors, which may compromise their health. The special requirements of migrants should be recognized in health care.     

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.     

Detection of genetic variance in blood pressure of seven-year-old twins

Results from twin studies in older children and adults indicate that there is significant genetic variance for blood pressure (BP). Utilizing date which were collected in 12 US university-affiliated hospitals in 1966-1973 in the Collaborative Perinatal Project (NCPP), the authors sought to determine if the effects of heredity on BP variability are apparent in younger twins. BP was determined in 197 pairs of like-sexed twins at seven years of age. Significant genetic variability for diastolic blood pressure (DBP) was found in the twins, with a heritability estimate of 0.53. Systolic blood pressure (SBP) results tended in the same direction but were not statistically significant. The trends were comparable for both sexes and races. These findings suggest that even at a young age substantial genetic influences on DBP variability are detectable.     

双生子儿童贫血状况分析

目的通过分析双生子儿童贫血状况和贫血同病率,探讨其遗传和环境效应.方法选取5～19岁双生子228对,其中MZ(单卵双生子)142对,DZ(二卵双生子)86对,在DNA卵性鉴定基础上,以成对法计算同病一致率、调整BMI前后组内相关系数及遗传度.结果双生子儿童贫血检出率与一般人群无明显差异,贫血同病一致率分别为MZ 0.28,DZ 0.15,Hb(血红蛋白)遗传度为0.23.调整BMI前后MZ与DZ组内相关系数和遗传度无显著变化.结论儿童贫血状态受遗传及环境因素共同影响,环境效应更明显.     

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.     

Twin membership and breast cancer risk.

Pregnancy estrogens are substantially elevated in twin pregnancies and are likely to be more so in the case of dizygotic twins. If levels of pregnancy estrogens were positively related to breast cancer risk in the offspring, female twin members would be expected to be at slightly higher risk. Data from an international case-control study were utilized to assess this hypothesis. The analysis was based on 870 cases with breast cancer and 2,641 hospital controls from two sites: Glamorgan, Wales (1965-1967), and Boston, Massachusetts (1965-1966). Seventeen cases were members of twin pairs, and 8 of them had a twin brother; 33 controls were members of twin pairs and 14 had a twin brother. Among all women, the odds ratios for breast cancer were as follows: for twins with brothers, 1.54 (95% confidence interval (CI) 0.64-3.71); for twins with sisters, 1.30 (95% CI 0.58-2.92); and for all twins, 1.40 (95% CI 0.77-2.55). The odds ratios were higher among premenopausal women. These findings are not conclusive, but they are compatible with the hypothesis that pregnancy estrogens may affect the risk of breast cancer in the offspring.     

中国9省(市)成年双生子体重指数遗传度估计

目的 探讨中国9省(市)成年双生子BMI遗传度情况。方法 收集中国双生子登记系统9省(市)成年双生子信息, 采用结构方程模型计算11 122对双生子BMI遗传度。结果研究对象中同卵双生子6 226对, 异卵双生子4 896对, 年龄范围25～85(39.0±10.8)岁。按地区分层, 男性BMI遗传度最高的是天津, 为67.8%(95%CI:50.1%～85.8%), 最低的是浙江, 为42.1%(95%CI:27.2%～60.9%);女性最高的是四川, 为56.2%(95%CI:47.5%～70.0%), 最低的是黑龙江, 为11.2%(95%CI:0～31.7%)。按性别分层, 相同地区的男性BMI遗传度均高于女性, 其中黑龙江男性和女性的遗传度差异最大, 分别为55.3%(95%CI:35.5%～80.0%)和11.2%(95%CI:0～31.7%), 而四川男性和女性的遗传度差异最小, 分别为61.5%(95%CI:40.7%～86.4%)和56.2%(95%CI:47.5%～70.0%)。结论 中国不同地区和不同性别人群BMI遗传度存在差别。