Determinants of infant growth in four age windows: a twin study.

OBJECTIVE: To identify determinants of growth during infancy. STUDY DESIGN: The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months). RESULTS: Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month (P < .0001). The effect size decreased with age until -0.02 (P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 (P = .001) to 0.06 (P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month (P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months (P = .002). CONCLUSION: From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.

Leisure-time physical activity and nutrition: a twin study.

OBJECTIVE: To determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years. DESIGN: Co-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests. SETTING: Finland. SUBJECTS: Sixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differences in eating behaviours. RESULTS: The eating habits questionnaire revealed that physically active co-twins more frequently reported that it is easy to eat according to need, whereas overeating and/or restrictive eating was more common among the inactive co-twins (P = 0·035). Avoiding calories was more common among the active than inactive co-twins (P = 0·034). Based on food diaries the physically active co-twins had daily energy intake on average 15·5 kJ/kg higher than their inactive co-twins (P = 0·030). The active co-twins also had a higher intake of vitamin C (P = 0·004), total water (P = 0·044), legumes and nuts (P = 0·015) and sweets (P = 0·036), as well as a lower energy-adjusted intake of meat (P = 0·013). CONCLUSIONS: The physically active persons seem to eat more but not necessarily healthier food. However, habitual physical activity may help in eating according to need and in reaching and maintaining a healthy body composition. Therefore, it is necessary to incorporate both dietary and physical activity advice into health counselling.

Birth weight discordance of twin pairs and their subsequent growth patterns.

BACKGROUND: Few studies have compared the growth of a twin with its co-twin and particularly in relation to birth weight discordance. AIM: The study investigated how the degree of birth weight discordance affected subsequent growth. METHODS: Birth weight discordance of 762 twin pairs was determined. Subsequent weight, height and occipital-frontal head circumference (OFC) measurements were obtained between the ages of 2-9 years. Corresponding standard deviations scores (SDS) were analysed according to birth weight discordance, sex and zygosity. Weight status was taken into account by assigning twins into sub-groups according to whether they were the heavier twin at birth and remained heavier, became the lighter of the twin pair or had the same weight, for subsequent measurements. RESULTS AND CONCLUSIONS: The degree of birth weight discordance had little effect on subsequent growth except in monozygotic (MZ) twins with >20% discordance. Severe low birth weight ( < 1.95 kg) is more significant in suppressing subsequent growth than the degree of discordance per se. A surprisingly high proportion of twins reversed their weight status when reviewed at an older age.

Sex ratios: human twins and fraternal effects.

Historical data from Finnish populations reveals that, for females, exposure to a male twin in the womb may have significant, life-long, effects on subsequent fitness, with profound implications for the evolution of sex ratios and brood size.

Preliminary evidence that estradiol moderates genetic influences on disordered eating attitudes and behaviors during puberty.

BACKGROUND: Puberty moderates genetic influences on disordered eating attitudes and behaviors, with little genetic influence before puberty but large (50%) genetic effects during and after puberty. To date, however, nothing is known about the mechanisms that underlie these effects. Estradiol is a particularly promising candidate, as estrogens become elevated at puberty and regulate gene transcription within neurotransmitter systems important for eating-related phenotypes. The aim of this pilot study was to examine whether estradiol levels moderate genetic influences on disordered eating during puberty. METHOD: Participants included 198 female twins (ages 10-15 years) from the Michigan State University Twin Registry. Disordered eating attitudes and behaviors were assessed with the total score, weight preoccupation, body dissatisfaction and binge eating/compensatory behavior subscales of the Minnesota Eating Behavior Survey (MEBS). Afternoon saliva samples were assayed for estradiol levels. Moderation of genetic effects was examined by comparing twin correlations in low versus high estradiol groups. RESULTS: In the low estradiol group, monozygotic (MZ) and dizygotic (DZ) twin correlations for all MEBS scales were similar, suggesting little genetic influence. In the high estradiol group, the MZ twin correlation was more than double the DZ twin correlation, indicating the presence of genetic effects. Findings could not be accounted for by age, body mass index or the physical changes of puberty. CONCLUSIONS: Estradiol may be one important moderator of genetic effects on disordered eating during puberty. Larger twin studies are needed to replicate this pilot work and quantify the extent of genetic moderation.

Monozygotic twins are discordant for chronic periodontitis: clinical and bacteriological findings.

OBJECTIVES: The aim of this study was to assess, in monozygotic (MZ) and dizygotic (DZ) twin pairs in whom the proband of the twin pair was suffering from moderate to severe chronic periodontitis, the contribution of genetics, periodontal pathogens and lifestyle factors towards the clinical phenotype. MATERIAL AND METHODS: For this study, 18 adult twin pairs were selected on the basis of interproximal attachment loss (AL) >or=5 mm in >or=2 non-adjacent teeth in one twin member. The study included 10 MZ and eight DZ twin pairs, in whom the periodontal condition, presence of periodontal pathogens, educational level, smoking behaviour and body mass index (BMI) were evaluated. RESULTS: Both MZ and DZ twins were discordant regarding AL and alveolar bone loss. Discordance was greater in DZ compared with MZ twins. In MZ twins, the discordance could not be explained by education, smoking, BMI and periodontal pathogens. In DZ twins, 45.6% of the discordance could be explained by more pack-years of the probands. CONCLUSION: The results confirm a possible role of genetic factors in periodontitis. However, the magnitude of the genetic effects on disease severity may have been overestimated previously.

Physical features observation: is it repeatable in zygosity determination of Chinese adult twins?

This study reports on the inter- and intrarater reliability of physical features observation. Study subjects were 176 Chinese adult persons, consisting of 89 males and 87 females. Three trained research assistants responded simultaneously and respectively to 12 items regarding the subject's physical features including 'hair', 'Mongoloid folds', left and right 'ear lobes', 'earwax', 'nostril shape', 'tongue rolling', left and right 'hitchhiker's thumb', 'mid-digital hair' and left and right 'simian crease' at the moment of interview. And 14 days later, these subjects received the same observation once again. The results showed that the inter- and intra-observer agreements of 'hair', 'earwax', 'tongue rolling', 'mid-digital hair' and 'simian crease' were almost perfect with most kappa (kappa) coefficients >or= .80, while 'Mongoloid fold' and 'nostril shape' showed poor inter-observer agreement and 'nostril shape' showed poor intra-observer agreement (kappa < .40). Two other physical features, 'hitchhiker's thumb' and 'ear lobes' showed moderate inter-observer agreement and three features, 'hitchhiker's thumb', 'ear lobes' and 'Mongoloid fold', showed moderate intra-observer agreement (.40

A longitudinal study on genetic and environmental influences on leisure time physical activity in the Finnish Twin Cohort.

The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18-54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (r(g) = 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (r(e) = 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (r(g) = 0.79) than women (r(g) = 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62 % and women 69%. The environmental correlations between the two time points were similar for men (r(e)= 0.21) and for women (r(e)= 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.

Male twins reduce fitness of female co-twins in humans.

In mammals, including humans, female fetuses that are exposed to testosterone from adjacent male fetuses in utero can have masculinized anatomy and behavior. However, the reproductive consequences of such prebirth sex-ratio effects for offspring and their implications for maternal fitness remain unexplored. Here we investigate the effects of being gestated with a male co-twin for daughter lifetime reproductive success, and the fitness consequences for mothers of producing mixed-sex twins in preindustrial (1734-1888) Finns. We show that daughters born with a male co-twin have reduced lifetime reproductive success compared to those born with a female co-twin. This reduction arises because such daughters have decreased probabilities of marrying as well as reduced fecundity. Mothers who produce opposite-sex twins consequently have fewer grandchildren (and hence lower fitness) than mothers who produce same-sex twins. Our results are unlikely to be a consequence of females born with male co-twins receiving less nutrition because such females do not have reduced survival and increases in food availability fail to improve their reproductive success. Nor are our results explained by after-birth social factors (females growing up with similarly aged brothers) because females born with a male co-twin have reduced success even when their co-twin dies shortly after birth and are raised as singletons after birth. Our findings suggest that hormonal interactions between opposite-sex fetuses known to influence female morphology and behavior can also have negative effects on daughter fecundity and, hence, maternal fitness, and bear significant implications for adaptive sex allocation in mammals.

Middle cerebral artery-peak systolic velocity in dizygotic twins with anti-E alloimmunization.

Middle cerebral artery-peak systolic velocity (MCA-PSV) has been reported to predict fetal anemia with similar accuracy as amniotic ΔOD450 assay. Alloimmunized dizygotic twin pregnancy allows us to compare anemic and non-anemic twins in the same intrauterine environment. We herein present a case of Rh (E)-incompatible dizygotic twin pregnancy, where MCA-PSV could precisely detect the anemia in one of the twins. A 36-year-old woman, whose previous child required exchange transfusion due to hemolytic anemia of newborn (HFDN), conceived twins after in vitro fertilization-embryo transfer. At 24 weeks' gestation, MCA-PSV of twin A and twin B were 23.9 cm/s (0.8 multiples of median; MoM) and 30.7 cm/s (1.0 MoM), respectively. At 31 weeks' gestation, MCA-PSV values of both twins were sharply elevated to nearly 1.4 MoM. Thereafter, MCA-PSV of twin A fell to 1.0 MoM, whereas MCA-PSV of twin B exceeded 1.5 MoM at 34 weeks' gestation. Development of fetal anemia was suspected and emergency cesarean section was performed. Twin B showed moderate anemia with positive direct Coombs' test and was diagnosed as HFDN due to anti-E alloimmunization. Twin B required phototherapy and red cell transfusion, but exchange transfusion was safely obviated.

Heritability of left ventricular and papillary muscle heart size: a twin study with cardiac magnetic resonance imaging.

AIMS: Earlier studies in monozygotic (MZ) and dizygotic (DZ) twins showed genetic variance on echocardiographically determined heart size. However, cardiovascular magnetic resonance (CMR) is more precise and reproducible. We performed a twin study relying on CMR, focusing on left ventricular (LV) mass and papillary muscle, since there are no genetic reports on this structure. METHODS AND RESULTS: We measured left heart dimensions of 25 healthy twin pairs with a 1.5T MR scanner, analysed with the mass, Medis Software. We performed heritability analysis and tests for genetic influences shared between cardiac structures. We found that CMR-based heritability estimates (h(2) = 84%) substantially exceeded estimates based on echocardiography. We also found significant genetic influence on papillary muscle mass (h(2) = 82%). Bivariate analysis of papillary and LV muscle mass revealed significant genetic influences shared by both phenotypes (genetic correlation 0.59) and suggested an additional genetic component specific to papillary muscle. We observed correlations between body mass index, surface area, and systolic blood pressure with cardiac dimensions, even in this small study. Environmental influences were relevant as well, indicating reciprocal influences on papillary vs. LV muscle mass. CONCLUSION: Cardiovascular magnetic resonance, even with few subjects, allows a genetic assessment of cardiac structures that cannot be attained with echocardiography. Hitherto fore unappreciated relationships can be uncovered by this method.

The electroencephalographic fingerprint of sleep is genetically determined: a twin study.

Humans have an individual profile of the electroencephalographic power spectra at the 8 to 16 Hz frequency during non-rapid eye movement sleep that is stable over time and resistant to experimental perturbations. We tested the hypothesis that this electroencephalographic "fingerprint" is genetically determined, by recording 40 monozygotic and dizygotic twins during baseline and recovery sleep after prolonged wakefulness. We show a largely greater similarity within monozygotic than dizygotic pairs, resulting in a heritability estimate of 96%, not influenced by sleep need and intensity. If replicated, these results will establish the electroencephalographic profile during sleep as one of the most heritable traits of humans.

Traces of embryogenesis are the same in monozygotic and dizygotic twins: not compatible with double ovulation.

Common knowledge of over a century has it that monozygotic and dizygotic twinning events occur by unrelated mechanisms: monozygotic twinning 'splits' embryos, producing anomalously re-arranged embryogenic asymmetries; dizygotic twinning begins with independent ovulations yielding undisturbed parallel embryogeneses with no expectation of departures from singleton outcomes. The anomalies statistically associated with twin births are due to the re-arranged embryos of the monozygotics. Common knowledge further requires that dizygotic pairs are dichorionic; monochorionicity is exclusive to monozygotic pairs. These are fundamental certainties in the literature of twin biology. Multiple observations contradict those common knowledge understandings. The double ovulation hypothesis of dizygotic twinning is untenable. Girl-boy twins differ subtly from all other humans of either sex, absolutely not representative of all dizygotics. Embryogenesis of dizygotic twins differs from singleton development at least as much as monozygotic embryogenesis does, and in the same ways, and the differences between singletons and twins of both zygosities represent a coherent system of re-arranged embryogenic asymmetries. Dizygotic twinning and monozygotic twinning have the same list of consequences of anomalous embryogenesis. Those include an unignorable fraction of dizygotic pairs that are in fact monochorionic, plus many more sharing co-twins' cells in tissues other than a common chorion. The idea that monozygotic and dizygotic twinning events arise from the same embryogenic mechanism is the only plausible hypothesis that might explain all of the observations.

Genetic and environmental effects on isometric muscle strength and leg extensor power followed up for three years among older female twins.

The purpose of this study was to examine changes in the contribution of genetic and environmental effects to isometric knee extensor strength and leg extensor power among 63- to 76-year-old female twins over a 3-yr follow-up. At baseline in 2000 the sample comprised 206 monozygotic (MZ) and 228 dizygotic (DZ) twin individuals, and at follow-up in 2003 the sample comprised 149 MZ and 164 DZ twin individuals. Genetic modeling showed that genetic effects explained 58% (95% CI: 46-68%) of the variance in muscle strength at baseline and 56% (95% CI: 41-68%) at follow-up, with no occasion-specific genetic effect. Nonshared environmental effects accounted for 42% (95% CI: 32-54%) of the variation at baseline and 15% (95% CI: 7-26%) at follow-up. In addition, new nonshared environmental effects explained the remaining variance, 29% (95% CI: 22-37%) of muscle strength at follow-up. For muscle power, the same genetic effects accounted for 67% (95% CI: 57-74%) of the variation at baseline and 48% (95% CI: 34-61%) at follow-up. Nonshared environmental effects in common at both measurement points explained 33% (95% CI: 25-43%) of the total variation at baseline and 11% (95% CI: 5-21%) at follow-up. The remaining variance of muscle power at follow-up was accounted for by time-specific environmental effects. Results indicated that the contribution of genetic effects to isometric muscle strength was stable, whereas for leg extensor power the proportion of genetic effects decreased during the follow-up. We observed new specific environmental effects underlying follow-up muscle strength and power, which effects could be due to the onset of new disease processes or changes in lifestyle.

Nature versus nurture in ventral visual cortex: a functional magnetic resonance imaging study of twins.

Using functional magnetic resonance imaging, we estimated neural activity in twins to study genetic influences on the cortical response to categories of visual stimuli (faces, places, and pseudowords) that are known to elicit distinct patterns of activity in ventral visual cortex. The neural activity patterns in monozygotic twins were significantly more similar than in dizygotic twins for the face and place stimuli, but there was no effect of zygosity for pseudowords (or chairs, a control category). These results demonstrate that genetics play a significant role in determining the cortical response to faces and places, but play a significantly smaller role (if any) in the response to orthographic stimuli.

Genetic contributions to long-range temporal correlations in ongoing oscillations.

The amplitude fluctuations of ongoing oscillations in the electroencephalographic (EEG) signal of the human brain show autocorrelations that decay slowly and remain significant at time scales up to tens of seconds. We call these long-range temporal correlations (LRTC). Abnormal LRTC have been observed in several brain pathologies, but it has remained unknown whether genetic factors influence the temporal correlation structure of ongoing oscillations. We recorded the ongoing EEG during eyes-closed rest in 390 monozygotic and dizygotic twins and investigated the temporal structure of ongoing oscillations in the alpha- and beta-frequency bands using detrended fluctuation analysis (DFA). The strength of LRTC was more highly correlated in monozygotic than in dizygotic twins. Statistical analysis attributed up to approximately 60% of the variance in DFA to genetic factors, indicating a high heritability for the temporal structure of amplitude fluctuations in EEG oscillations. Importantly, the DFA and EEG power were uncorrelated. LRTC in ongoing oscillations are robust, heritable, and independent of power, suggesting that LRTC and oscillation power are governed by distinct biophysical mechanisms and serve different functions in the brain. We propose that the DFA method is an important complement to classical spectral analysis in fundamental and clinical research on ongoing oscillations.

Relation of birth weight, body mass index, and change in size from birth to adulthood to insulin resistance in a female twin cohort.

CONTEXT AND OBJECTIVES: Because an adverse intrauterine environment is thought to induce insulin resistance, our objective was to investigate the relationships between birth weight, BMI, and change in body size over the life course and insulin resistance. SETTING, DESIGN, AND PARTICIPANTS: We conducted a cross-sectional study in a cohort of 1194 female twins aged 18-74 yr. The relationship between birth weight and insulin resistance was analyzed using a regression method allowing for a simultaneous estimation of within- and between-pair influences. The approach allows the influence of individual fetal nutrition on adult insulin resistance to be distinguished from effects that are mediated by confounding factors in the maternal environment. MAIN OUTCOME MEASURES: Insulin resistance was measured by the homeostasis model assessment. RESULTS: Individual level regression analyses showed no significant relationship between birth weight and insulin resistance. There was a significant positive relationship between insulin resistance and current body mass index (BMI) (a 26% increase in insulin resistance per sd increase in BMI; confidence interval, 22.6-29.5%). This significant relationship was accounted for in equal parts by individual-specific effects and by confounding factors in the shared environment of the twins. The relationship with birth weight became significant only after adjustment for BMI and was mediated only through between-pair differences. CONCLUSIONS: These results suggest that insulin resistance is influenced more by current body size than birth weight and that postnatal growth is potentially more important than fetal growth in the subsequent development of insulin resistance.

Genetic loci linked to pituitary-thyroid axis set points: a genome-wide scan of a large twin cohort.

OBJECTIVE: Previous studies have shown that circulating concentrations of TSH, free T4, and free T3 are genetically regulated, but the genes responsible remain largely unknown. The aim of this study was to identify genetic loci associated with these parameters. DESIGN: We performed a multipoint, nonparametric genome-wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history of thyroid disease. The genome scan comprised 737 microsatellite markers supplemented with dinucleotide markers. Data were analyzed using residualized thyroid hormone data after adjustment for age, smoking, and body mass index. RESULTS: Multipoint linkage analysis gave linkage peaks for free T4 on chromosome 14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32, and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0-2.3). CONCLUSIONS: This study has identified eight genomic locations with linkage of LOD of 2.0 or greater. These results should enable targeted positional candidate and positional cloning studies to advance our understanding of genetic control of the pituitary-thyroid axis.

Associations between long-term physical activity, waist circumference and weight gain: a 30-year longitudinal twin study.

BACKGROUND AND OBJECTIVE: Physical activity level and obesity are both partly determined by genes and childhood environment. To determine the associations between long-term leisure-time physical activity, weight gain and waist circumference and whether these are independent of genes and childhood effects. DESIGN AND SUBJECTS: The study design is a 30-year follow-up twin study in Finland. For this study, 146 twin pairs were comprehensively identified from the large Finnish Twin Cohort. These twin pairs were discordant for both intensity and volume of leisure physical activity in 1975 and 1981 and were healthy in 1981. At follow-up in 2005, both members of 89 pairs were alive and participated in a structured telephone interview. In the interview self-measured weight and waist circumference, and physical activity level for the whole follow-up were assessed. Paired tests were used in the statistical analyses. MAIN OUTCOME MEASURES: Waist circumference at 30-year follow-up (2005) and change in weight from 1975 to 2005. RESULTS: In the 42 twin pairs discordant for physical activity at all time points during the 30-year period, the mean weight gain from 1975 through 2005 was 5.4 kg (95% confidence interval (CI) 2.0-8.9) less in the active compared to inactive co-twins (paired t-test, P=0.003). In 2005, the mean waist circumference was 8.4 cm (95% CI 4.0-12.7) less in the active compared with inactive co-twins (P<0.001). These trends were similar for both monozygotic and dizygotic twin pairs. Pairwise differences in weight gain and waist circumference were not seen in the 47 twin pairs, who were not consistently discordant for physical activity. CONCLUSION: Persistent participation in leisure-time physical activity is associated with decreased rate of weight gain and with a smaller waist circumference to a clinically significant extent even after partially controlling for genetic liability and childhood environment.