An adverse intra-uterine environment has been associated with abdominal fat distribution in singletons. Twins often have a low birth weight and a short gestation. Therefore, they may have an increased risk to develop abdominal obesity. Furthermore, monozygotic monochorionic twins (MZ MC) have a larger intra-pair birth weight difference compared to monozygotic dichorionic twins (MZ DC). If adult anthropometry is programmed in utero, this may affect the intra-pair correlations in adulthood and, consequently, also the results from the classic twin method to estimate genetic and environmental influences. In the present study, we compared the absolute values, the intra-pair differences, and the intra-pair correlations of body mass, height, BMI, and abdominal fat distribution of 424 MZ MC, MZ DC and dizygotic (DZ) twin pairs (aged 18–34 yrs). DZ, MZ DC and MZ MC twins did not differ for most anthropometric characteristics. Only MZ women tended (p = 0.03) to accumulate more abdominal fat compared to DZ twins. Overall, the contribution of zygosity and chorion type to adult anthropometry was rather low (≤ 1.7%). Although the intra-pair birth weight difference of MZ MC pairs (10.5% in men, 12.3% in women) was significantly larger compared to that of MZ DC pairs (6.9% and 9.2% resp.), the intra-pair differences in adult anthropometry were similar for both MZ twin types. Also the intra-pair correlations of MZ MC and MZ DC pairs were strikingly alike, suggesting no significant influence of the prenatal environment on adult concordance. In conclusion, the substantial difference in the prenatal environment of MZ MC and MZ DC twins did not result in a difference in intra-pair concordance of adult anthropometry and fat distribution. Therefore, we suggest that the chorion type of MZ twins does not bias the twin design and the estimation of the genetic contribution to adult anthropometry.

Assisted reproductive techniques have led to an increase in the proportion of maternities that are multiple. Though predominantly dizygotic, they are at greater risk of monozygotic division than those spontaneously conceived. England and Wales data 1974–99 on stillbirths and livebirths were analysed for 4 periods: 1974–80 (pre-assisted reproduction; 1982–8; 1989–91 (pre-redefinition of stillbirth); 1993–9 (post-redefinition of stillbirth). For twin data, Weinberg's rule was applied to estimate the proportions that were mono- (MZ) and dizygotic (DZ). Compared with the period before assisted reproduction, the most recent period shows an increase in twin maternities of 3.81 per 1000 comprised of 3.22 (95% CI 3.10 to 3.33; p < 0.0001) DZ and 0.60 (95% CI 0.51 to 0.68; p < 0.0001) MZ twins. It is estimated that 15.7% of assisted reproduction twins are MZ. Higher order multiple births showed an increase of 3.06 (95% CI 2.85 to 3.29; p < 0.0001) per 10,000 maternities. Stillbirth rates in MZ twins are of the same order of magnitude as those in higher order multiple births but higher than those in DZ twins. The improvement in stillbirth rates over the 26 year study period is of the same order magnitude in singletons, DZ and MZ twins and higher order multiples. Assisted reproduction has led to a significant increase in the proportion of MZ twins. These are at high risk of fetal death and this needs to be considered when local stillbirth and perinatal mortality rates are used in auditing obstetric services.

In recent years, there has been a renewed interest in the relationship between intelligence and personality. Extraversion, in particular, has been suggested to influence intelligence, but the direction of this relationship has been controversial (Wolf & Ackerman, 2005). In a young adult sample, the NEO PI-R was completed by 103 pairs of monozygotic twins, 181 pairs of dizygotic twins and 210 of their nontwin siblings. IQ data (Multidimensional Aptitude Battery) were available for approximately three quarters of this sample, and were collected at 16 years as part of an ongoing study of cognition conducted by the Queensland Institute of Medical Research. All extraversion facets were significantly influenced by genes with both additive and nonadditive genetic effects being important (heritabilities ranged from .25 for activity to .54 for warmth). While a significant correlation between the extraversion domain score and IQ was not found, the extraversion facet of excitement-seeking (E5) was significantly negatively correlated with both verbal (r = −.15) and performance (r = −.11) IQ scores. The facet of gregariousness was significantly correlated with verbal IQ only (r = −.09). The relationship between excitement-seeking and IQ was further shown to be solely due to additive genetic influences. These common genetic effects may stem from a dependence on brain dopamine, a neurotransmitter that has been implicated in both personality and cognition.

Circulating levels of leptin and adiponectin are closely associated with obesity. However, it is not known whether there are common shared genes or environment exerting influences on the levels of leptin, adiponectin, and BMI. We aimed to assess the relative contribution of genes and environment to adiponectin, leptin, and BMI individually as well as simultaneously to the three measures. Our subjects included a total of 228 twin/sibling pairs aged 12 to 18 (130 monozygotic twins, 68 dizygotic twins and 30 sibling pairs) were recruited from the middle schools. Multivariate analyses were applied to twin/sibling data using structural equation modeling. The results showed that intraclass correlations for adiponectin, leptin and BMI were higher in the MZ twins than those in the DZ/SP group. The relative contribution of genes to adiponectin (39%) was comparable to those of shared environment (40%). In contrast, leptin and BMI were influenced mostly by genes (74% and 89%, respectively). The multivariate genetic analyses showed that a latent factor underlying the three measures was identified, with BMI being equivalent to this latent factor. The BMI-dependent genetic factor explains only 15% and 34% of variation of adiponectin and leptin, respectively. These data indicate a differential contribution of genetic factors for the variation of adiponectin, leptin and BMI. More importantly, only a small portion of the genetic influences on adiponectin and leptin was attributed to BMI. Our findings provided more insight into the complex regulation of adiponectin and leptin in obesity.

In this article, we present the genomic DNA yield and the microsatellite and single nucleotide polymorphism (SNP) genotyping success rates of genomic DNA extracted from a large number of mouth swab samples. In total, the median yield and quality was determined in 714 individuals and the success rates in 378,480 genotypings of 915 individuals. The median yield of genomic DNA per mouth swab was 4.1 μg (range 0.1–42.2 μg) and was not reduced when mouth swabs were stored for at least 21 months prior to extraction. A maximum of 20 mouth swabs is collected per participant. Mouth swab samples showed in, respectively, 89% for 390 microsatellites and 99% for 24 SNPs a genotyping success rate higher than 75%. A very low success rate of genotyping (0%–10%) was obtained for 3.2% of the 915 mouth swab samples using microsatellite markers. Only 0.005% of the mouth swab samples showed a geno-typing success rate lower than 75% (range 58%–71%) using SNPs. Our results show that mouth swabs can be easily collected, stored by our conditions for months prior to DNA extraction and result in high yield and high-quality DNA appropriate for genotyping with high success rate including whole genome searches using microsatellites or SNPs.

Using univariate sum scores in genetic studies of twin data is common practice. This practice precludes an investigation of the measurement model relating the individual items to an underlying factor. Absence of measurement invariance across a grouping variable such as gender or environmental exposure refers to group differences with respect to the measurement model. It is shown that a decomposition of a sum score into genetic and environmental variance components leads to path coefficients of the additive genetic factor that are biased differentially across groups if individual items are non-invariant. The arising group differences in path coefficients are identical to what is known as “scalar sex limitation” when gender is the grouping variable, or as “gene by environment interaction” when environmental exposure is the grouping variable. In both cases the interpretation would be in terms of a group-specific effect size of the genetic factor. This interpretation may be incorrect if individual items are non-invariant.

The purpose of this study was to clarify the characteristic child-rearing problems for mothers of multiple children who conceived after infertility treatment as compared to mothers of multiple children who conceived spontaneously. The subjects were 990 mothers of multiple children: 359 who conceived after infertility treatment and 631 who conceived spontaneously. Mothers who conceived after infertility treatment were more delighted when informed of a multiple pregnancy than those who conceived spontaneously. In addition, with respect to anxiety during twin pregnancies, mothers of twins who conceived after infertility treatment showed lower rates of anxiety about nursing the infants and economic concerns than those of twins who conceived spontaneously. However, after delivery, mothers who conceived after infertility treatment showed a higher rate of depressive symptoms than those who conceived spontaneously. After adjusting for each associated factor using logistic regression, the risk of depressive symptoms in mothers who conceived after infertility treatment was significantly associated with disabled multiple children and the methods for alleviating stress. The odds ratio indicated that mothers with at least one disabled child were twice as likely to have depressive symptoms as mothers with no disabled children. Furthermore, the odds ratio indicated that mothers who used no methods for alleviating stress were twice as likely to have depressive symptoms than those who did.

Genetic and environmental factors contribute to the etiology of anorexia nervosa (AN). The co-twin control design is one of the most powerful methods available to evaluate environmental factors that could contribute to differences between monozygotic (MZ) twins who are discordant for AN. Using available data from a unique and rare sample of 22 Swedish female MZ pairs discordant for AN, we compared personality, life events, comorbidity, and health factors. Twins with AN had significantly higher perfectionism scores than unaffected co-twins and reported younger ages at first diet than unaffected co-twins who had dieted. Consistent with previous literature, more twins with AN reported gastrointestinal problems than unaffected co-twins. Although not significant due to low statistical power, more unaffected co-twins reported experiencing emotional neglect than twins with AN. Early dieting may be a harbinger of the development of AN or an early symptom. Higher perfectionism may represent a risk factor, sequela, or both. Sibling perception of neglect is noteworthy given the impact of an ill child with AN on family function and wellbeing. The health and wellbeing of siblings should be addressed clinically when one child in the family suffers from AN.

The amount of available DNA is often a limiting factor in pursuing genetic analyses of large-scale population cohorts. An association between higher DNA yield from blood and several phenotypes associated with inflammatory states has recently been demonstrated, suggesting that exclusion of samples with very low DNA yield may lead to biased results in statistical analyses. Whole genome amplification (WGA) could present a solution to the DNA concentration-dependent sample selection. The aim was to thoroughly assess WGA for samples with low DNA yield, using the multiply-primed rolling circle amplification method. Fifty-nine samples were selected with the lowest DNA yield (less than 7.5µg) among 799 samples obtained for one population cohort. The genotypes obtained from two replicate WGA samples and the original genomic DNA were compared by typing 24 single nucleotide polymorphisms (SNPs). Multiple genotype discrepancies were identified for 13 of the 59 samples. The largest portion of discrepancies was due to allele dropout in heterozygous genotypes in WGA samples. Pooling the WGA DNA replicates prior to genotyping markedly improved genotyping reproducibility for the samples, with only 7 discrepancies identified in 4 samples. The nature of discrepancies was mostly homozygote genotypes in the genomic DNA and heterozygote genotypes in the WGA sample, suggesting possible allele dropout in the genomic DNA sample due to very low amounts of DNA template. Thus, WGA is applicable for low DNA yield samples, especially if using pooled WGA samples. A higher rate of genotyping errors requires that increased attention be paid to genotyping quality control, and caution when interpreting results.

Non-shared parenting and deviant peer affiliation are linked to differences in externalizing behaviors between twins. However, few studies have examined these two non-shared environments simultaneously. The present study examined the transactional roles of differential parenting (i.e., warmth and hostility) and deviant peer affiliation on monozygotic (MZ) twin differences in externalizing behaviors using a two-wave longitudinal study of twins and their parents. The sample consisted of 520 pairs of MZ twins (46.5% males, 53.5% females), with a mean age of 13.86 years (SD = 2.10) at the T1 assessment, residing in Beijing, China. The association between non-shared hostility in parenting and adolescent externalizing behaviors was mainly explained by a child-driven effect whereby the twin with a higher level of externalizing behaviors than his or her co-twin was more likely to receive more hostility from the parents. Similarly, the relationship between deviant peer affiliation and adolescent externalizing behaviors supported the selection effect whereby the twin with a higher level of externalizing behaviors than his or her co-twin was more likely to affiliate with deviant peers. The theoretical and practical implications of these findings are discussed.

Previous studies in young and adolescent twins suggested substantial genetic contributions to the amplitude and latency of the P3 evoked by targets in an oddball paradigm. Here we examined whether these findings can be generalized to adult samples. A total of 651 twins and siblings from 292 families participated in a visual oddball task. In half of the subjects the age centered around 26 (young adult cohort), in the other half the age centered around 49 (middle-aged adult cohort). P3 peak amplitude and latency were scored for 3 midline leads Pz, Cz, and Fz. No cohort differences in heritability were found. P3 amplitude (∼50%) and latency (∼45%) were moderately heritable for the 3 leads. A single genetic factor influenced latency at all electrodes, suggesting a single P3 timing mechanism. Specific genetic factors influenced amplitude at each lead, suggesting local modulation of the P3 once triggered. Genetic analysis of the full event-related potential waveform showed that P3 heritability barely changes from about 100 ms before to 100 ms after the peak. Age differences are restricted to differences in means and variances, but the proportion of genetic variance as part of the total variance of midline P3 amplitude and latency does not change from young to middle-aged adulthood.

Objective: To compare the fetal loss rate of monochorionic (MC) twin pregnancies according to their amnionicity. Methods: A retrospective review of all MC pregnancy outcomes in a tertiary centre. Pregnancy outcomes were compared for monochorionic monoamniotic (MCMA) versus monochorionic diamniotic (MCDA) pregnancies. Results: 29 MCMA and 117 MCDA twin pregnancies were identified. The overall fetal loss rate was significantly higher in MCMA (23/52, 44.2%) compared to MCDA pregnancies (28/233, 12%, Chi squared = 30.03, p < .001). Kaplan-Meier analysis showed that fetal survival rate in MCDA twins were significantly higher than in MCMA twins (Log-rank Chi-squared = 27.9, p < .0005). Early pregnancy ultrasound identified the causes for these fetal losses in some MCMA twins. After exclusion of identifiable causes, the difference in fetal survival was not significant in the two groups (Log-rank chi-squared = 0.373, p = .54). Conclusion: The loss rate for MCMA twins is high and occurs mainly due to discordant congenital abnormality, conjoint twins or twin reversed arterial perfusion (TRAP) sequence. Although the fetal loss rate in MCDA is lower than in MCMA pregnancies, the majority of fetal loss in MCDA pregnancies cannot be predicted at the first scan at presentation. The data of this study questions the widespread policy of a difference in the scheduling of elective delivery for MCMA and MCDA twins.

The main aim of this study was to examine twin specific risk factors that influence educational achievement in primary school. We included prenatal factors that are not unique to twins, except for zygosity, but show a higher prevalence in twins than in singletons. In addition, educational achievement was compared between twins and their nontwin siblings in a within-family design. Data were obtained from parents and teachers of approximately 10,000 twins and their nontwin siblings registered with the Netherlands Twin Register. Teachers rated the proficiency of the children on arithmetic, language, reading, and physical education, and reported a national educational achievement test score (CITO). Structural equation modeling showed that gestational age, birth weight, and sex were significant predictors of educational achievement, even after correction for socioeconomic status. Mode of delivery and zygosity did not have an effect, while parental age only influenced arithmetic. Mode of conception, incubator time, and birth complications negatively affected achievement in physical education. The comparison of educational achievement of twins and singletons showed significantly lower ratings on arithmetic, reading, and language in twins, compared to their older siblings, but not compared to their younger siblings. Low gestational age and low birth weight were the most important risk factors for lower educational achievement of twins in primary school. It seems that the differences observed between twins and their nontwin siblings in educational achievement can largely be explained by birth order within the family.

The monocyte–lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-family population. Data were obtained in 9,501 individuals from the Netherlands Twin Register. We used regression analyses to determine the effects of age, sex, smoking, and body mass index (BMI) on MLR and its subcomponents. Data on twins, siblings and parents (N = 7,513) were analyzed by genetic structural equation modeling to establish heritability and genome wide single nucleotide polymorphism (SNP) data from a genotyped subsample (N = 5,892) and used to estimate heritability explained by SNPs. SNP and phenotype data were also analyzed in a genome-wide association study to identify the genes involved in MLR. Linkage disequilibrium (LD) score regression and expression quantitative trait loci (eQTL) analyses were performed to further explore the genetic findings. Results showed that age, sex, and age × sex interaction effects were present for MLR and its subcomponents. Variation in MLR was not related to BMI, but smoking was positively associated with MLR. Heritability was estimated at 40% for MLR, 58% for monocyte, and 58% for lymphocyte count. The Genome-wide association study (GWAS) identified a locus on ITGA4 that was associated with MLR and only marginally significantly associated with monocyte count. For monocyte count, additional genetic variants were identified on ITPR3, LPAP1, and IRF8. For lymphocyte count, GWAS provided no significant findings. Taking all measured SNPs together, their effects accounted for 13% of the heritability of MLR, while all known and identified genetic loci explained 1.3% of variation in MLR. eQTL analyses showed that these genetic variants were unlikely to be eQTLs. In conclusion, variation in MLR level in the general population is heritable and influenced by age, sex, and smoking. We identified gene variants in the ITGA4 gene associated with variation in MLR. The significant SNP-heritability indicates that more genetic variants are likely to be involved.

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.

Multiple birth remains prevalent, with prematurity and subsequent disability being common complications. However, little is known of the experiences of mothers living with the combined circumstances of multiple birth, prematurity, and special needs. This paper reports an exploratory study using the qualitative technique of thematic analysis, to describe and interpret the experiences of 10 mothers of prematurely born multiple birth children with diverse special needs. Mothers were shocked to learn they were carrying multiple fetuses, including those who underwent in vitro fertilization with dual embryo transfer. Most experienced protracted concern over one or more babies’ survival during pregnancy, and prescribed bed rest was frequently associated with increased anxiety and other adverse psychological effects. Some experienced disenfranchised grief, such as those grieving the opportunity to bear a single child. The contrast with experiences of mothers of healthy, term singletons caused considerable distress. Feelings of detachment and unreality were common in the immediate postpartum period, possibly due to transient depersonalization. Having more than one newborn created practical and psychological problems during the neonatal period, particularly when infants were separated due to differences in medical status. The extent to which hospitals accommodated the multiple birth relationship varied and significantly affected mothers’ postnatal experiences. Mothers often felt guilty, particularly regarding inequality of care and attention they were able to provide to each child. This was especially problematic for multiples discordant for special needs status. The presence of one normally developing child complicated adjustment to the other's difficulties, and several experienced chronic sorrow. Serious maternal mental health difficulties were common but not universal. Available formal supports were generally perceived as inadequate, addressing some, but not all, of the mothers’ needs. Further work is needed to advance understanding of the relationships between mothers and their multiples, and to explore the implications of special needs within multiple birth families.

Males and females score differently on some personality traits, but the underlying etiology of these differences is not well understood. This study examined genetic, environmental, and prenatal hormonal influences on individual differences in personality masculinity–femininity (M-F). We used Big-Five personality inventory data of 9,520 Swedish twins (aged 27 to 54) to create a bipolar M-F personality scale. Using biometrical twin modeling, we estimated the influence of genetic and environmental factors on individual differences in a M-F personality score. Furthermore, we tested whether prenatal hormone transfer may influence individuals’ M-F scores by comparing the scores of twins with a same-sex versus those with an opposite-sex co-twin. On average, males scored 1.09 standard deviations higher than females on the created M-F scale. Around a third of the variation in M-F personality score was attributable to genetic factors, while family environmental factors had no influence. Males and females from opposite-sex pairs scored significantly more masculine (both approximately 0.1 SD) than those from same-sex pairs. In conclusion, genetic influences explain part of the individual differences in personality M-F, and hormone transfer from the male to the female twin during pregnancy may increase the level of masculinization in females. Additional well-powered studies are needed to clarify this association and determine the underlying mechanisms in both sexes.

There is significant covariation between internalizing and externalizing behavior, although there is also evidence that internalizing behavior is a protective factor against externalizing behavior. Several researchers have posited that the examination of the relationship between temperament or personality and behavior problems may help explain these seemingly contradictory results. Specifically, negative emotionality or neuroticism has been cited as a temperament characteristic that internalizing and externalizing behavior share in common, whereas behavioral inhibition may be related only to internalizing behavior. We examined the degree to which the covariation between internalizing and externalizing behavior assessed from age 4 to 12 years can be explained by temperament characteristics assessed from age 14 to 36 months. Additionally, we assessed the extent to which this relationship is due to genetic or environmental factors, analyzing data from 225 monozygotic and 185 dizygotic twin pairs assessed by the Colorado Longitudinal Twin Study. In males, a portion of the covariation between internalizing and externalizing behavior was explained by shared environmental influences in common with emotionality and shared environmental influences in common with shyness. In females, most of the covariation between internalizing and externalizing behavior was explained by shared environmental influences in common with emotionality. A possible limitation of this study is that the covariation between temperament and behavior problems may be due to shared measurement variance, as parent ratings were used to assess both temperament and behavior problems.

The South Korean Twin Registry (SKTR) is an ongoing nation-wide volunteer registry of South Korean twins and their families, which was established in the year 2001 to understand genetic and environmental etiologies of psychological and physical traits among South Koreans. Recently, the SKTR sampling has been extended in two important ways. First, we began to recruit twins from lower socio-economic families to study interaction effects of gene by environmental context. Second, as a parallel study of the SKTR, the Nigerian Twin and Sibling Registry was developed to understand the origin of the population group differences/similarities in psychological traits between South Koreans and Nigerians. This article summarizes the main findings (based on the SKTR sample to date), recruitment procedures, zygosity assessment, measures, and future plans for the SKTR.

Aspects of disordered eating and personality traits, such as neuroticism, are correlated and individually heritable. We examined the phenotypic correlation between binge eating episodes and indices of personality (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness, and control/impulsivity). For correlations ≥|0.20|, we estimated the extent to which genetic and environmental factors contributed to this correlation. Participants included 3,446 European American same-sex female twins from the Missouri Adolescent Female Twin Study (median age = 22 years). Binge eating episode was assessed via interview questions. Personality traits were assessed by self-report questionnaires. There was a significant moderate phenotypic correlation between binge eating episode and neuroticism (r = 0.33) as well as conscientiousness (r = -0.21), while other correlations were significant but smaller (r ranging from -0.14 to 0.14). Individual differences in binge eating episodes, neuroticism, and conscientiousness were attributed to additive genetic influences (38% [95% CI: 21–53%], 45% [95% CI: 38–52%], and 44% [95% CI: 0.33–0.55%] respectively), with the remaining variance attributed to individual-specific environmental influences. Covariance was attributable to genetic (neuroticism r g = 0.37; conscientiousness r g = -0.22) and individual-specific environmental (neuroticism r e = 0.28; conscientiousness r e = -0.19) influences. Personality traits may be an early indicator of genetic vulnerability to a variety of pathological behaviors, including binge eating episode. Furthermore, prior research documenting phenotypic correlations between eating disorder diagnoses and personality may have stemmed from etiological overlap between these personality traits and aspects of disordered eating, such as binge eating episode.