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.     

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.     

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 impact of genes and pre- and postnatal environment on the metabolic syndrome. Evidence from twin studies

Our population-based Danish twin study demonstrated a genetic influence on several of the components included in the metabolic syndrome, i.e. glucose intolerance, overall obesity, systolic and diastolic blood pressure and low levels of HDL-cholesterol. Abdominal obesity, insulin resistance and hypertriglyceridaemia had, on the other hand, a relatively higher environmental aetiological component. Furthermore we demonstrated a difference in aetiology among male and female twins indicating an influence of sex on several of the components in the metabolic syndrome. Studies have demonstrated an impact of the intrauterine environment (i.e. low birth weight) for the development of the components in the metabolic syndrome. The validity of conclusions drawn from classical twin studies has therefore been questioned due to the different prenatal circumstances characterising monozygotic (MZ) and dizygotic (DZ) pregnancies. Due to a potentially more adverse intrauterine environment among MZ compared to DZ twins, MZ twins may be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profiles after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--together with higher levels of total-cholesterol and triglycerides among MZ compared to DZ twins demonstrate an effect of zygosity (i.e. intrauterine environment) on these metabolic variables and therefore question the assumption of equal pre- and postnatal environment in MZ and DZ twins. Our studies provide further evidence for a prenatal component in the aetiology of the components included in the syndrome and question the validity of classical twin studies on phenotypes with a known prenatal aetiological component. However, our present knowledge is currently far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of the metabolic and haemodynamic components included in the metabolic syndrome.     

双生子A型人格与高血压及血生化指标研究

目的 了解双生子A型人格与高血压及血液生化指标的关系。方法 利用遗传流行病学方法对青岛市89对24岁以上双生子(同卵55对，异卵34对)进行调查。并进行A型人格测试，以比较同卵与异卵双生于A型人格得分的相关程度、A型人格及血压的一致性。推测遗传与环境因素对A型人格的影响，A型人格与高血压的关系，并探讨血液生化指标与A型人格的关系。结果 经KAPPA一致性检验，同卵(MZ)双生子之间A型人格存在着显的一致性(P＜0．001)，而异卵(DZ)双生子之间的一致性无显性差异(P＝0．802)。同时，MZ双生子之间A型人格和血压也存在显的一致性(P＜0．001)，而DZ双生子之间A型人格和血压无明显一致性(P＝0．102)。有A型人格的双生子血压的收缩压明显高于非A型人格的双生子(P＜0．05)。许多生化指标与A型人格因素相关，但是所计算出的相关系数大都小于0．30，属于弱相关。结论 MZ双生子A型人格及高血压之间存在着显的一致性，而这种一致性在DZ双生子表现不明显。A型人格是高血压的危险因素之一。A型人格与所研究血液基本生化指标之间相关较弱。     

Socioeconomic position and twins' health: a life-course analysis of 1266 pairs of middle-aged Danish twins

BACKGROUND: The association between socioeconomic circumstances and health in adulthood could come about through processes that may be divided into factors experienced early in life and those experienced in later adulthood. In order to disentangle the influences on health of the early genetic, prenatal and rearing environmental factors from environmental factor later in life, we compared the health status among male and female twin pairs who lived together during childhood and were discordant or concordant on adult socioeconomic position. METHODS: A cross-sectional survey among a random sample of middle-aged Danish twins was conducted in 1998-99. The study population included 1266 like-sex twin pairs [52.5% monozygotic (MZ) and 47.6% dizygotic (DZ)]. Data were obtained on childhood and adult social class and on height, BMI, grip strength, depression symptoms, self-rated health, cognitive function, physical activity, smoking, alcohol and food intake. RESULTS: The expected associations between the individual twins' adult social class and health measures were observed. Among DZ male twins discordant on adult social class, the higher social class twin was on average significantly taller and had higher cognitive test scores. Among DZ female twins discordant on adult social class, the higher social class female twin was more physically active and had a higher cognitive test score. There were no significant health disparities or behavioural differences between the members of MZ twin pairs discordant on adult social class. For most health outcomes, the variability within twin pairs was related to zygosity (higher for DZ than for MZ) but not to social class. CONCLUSION: This study suggests that the relationship between adult social class and health outcomes in Denmark is due mainly to selection effects rather than a causal effect of social class exposures on health and behaviour.     

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.     

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.     

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)     

The epidemiology of anencephaly and spina bifida in Izmir, Turkey, in the light of recent aetiological theories

The data from this study suggest that, in western Turkey, potato consumption and water hardness do not play a significant role in the aetiology of anencephaly and spina bifida (ASB). Several of the predictions of the fetus-fetus interaction theory are not supported. Other predictions could not be tested because of lack of information on the dizygotic (DZ) twinning rate. Twin data from this study, together with previous material containing explicit information on zygosity, suggest that true concordance of a particular neural tube anomaly occurs only in monozygotic (MZ) twins. It also seems that even ASB concordance occurs in DZ twins only at a rate comparable with recurrence in siblings. This confirms the earlier refutation (Field and Kerr, 1974) of the supposition of Nance (1971) that MZ twin pairs are strikingly discordant for ASB compared with DZ pairs. However, the evidence seems to go further than Field's assertion that MZ and DZ pairs are affected about equally. Concordance in DZ twins is in comparison with sibling data, but MZ pairs show a significantly higher rate of concordance in both categories. Finally, the incidence of ASB in Izmir compared with the areas of ethnic origin of the Turks, and the high representation of families from Balkan areas where the incidence more closely resembles that of Izmir, suggest that the genetic factor is important in this area.     

139对双生子红细胞钠、钾离子的遗传度分析

利用遗传流行病学方法调查了天津市南开区139对双胞胎,其中单卵双生(MZ)74对,双卵双生(DZ)65对。并用几种不同的遗传度估计方法分析了红细胞Na⁺、K⁺的共同基因和共同环境因素对血压的影响。结果表明遗传因素、共同环境因素及双胞胎各自的环境因素对血压影响近似的是RBC Na⁺,h²=0.32,C²=0.35,u²=0.33。环境因素为主要原因的是RBC K⁺,C²=0.97。     

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.     

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

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

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。     

双生子的血清脂质和脂蛋白遗传度及影响因素分析

目的　分析儿童、青少年的血脂指标遗传度及影响因素。方法　选择 5～ 19岁双生子2 36对 ,平均年龄 (11 2± 3 4 )岁 ,其中同卵双生子 14 3对 ,异卵双生子 93对。在DNA卵性鉴定基础上 ,以组内相关系数法及Falconer公式计算调整年龄性别前后的遗传度 ,偏态数据进行对数转换 ;校正年龄性别 ,分析相关体格、生化指标对血脂的影响。结果　同卵与异卵双生子间甘油三酯对内方差及相关系数的差异均无显著性 ;总胆固醇、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)和脂蛋白 (a)对内方差及相关系数的差异有显著性 ,遗传度估计值分别为 0 5 6、0 5 5、0 4 9和 0 5 8,调整年龄性别后各指标估计遗传度分别为 0 6 3、0 6 3、0 5 5和 0 6 4。总胆固醇、HDL C、LDL C和脂蛋白(a)与年龄呈负相关 ;女孩的总胆固醇、HDL C、LDL C稍高于男孩。校正年龄性别后除脂蛋白 (a)外各血脂指标多数与体重指数、体脂率及培利迪西指数相关 ,与血压、血糖和血钙等也有相关性。结论　总胆固醇、HDL C、LDL C和脂蛋白 (a)受遗传因素影响较大 ,而甘油三酯主要受环境因素影响。儿童的血脂水平受年龄和性别的影响 ,与反映体脂和机体营养发育的指标相关。     

Lifestyle and blood pressure levels in male twins in Utah

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

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

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

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.     

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 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.