Renal cell carcinoma is an important clinical disease with poorly understood etiology. ELF5 is an epithelial-specific member of the Ets family of transcription factors, characterized by the 80 amino acid Ets domain that binds the purine-rich GGAA/T Ets motif found in the promoter regions of a variety of genes. Since ELF5 is highly expressed in kidney and has been postulated to function as a tumor suppressor, at least in the context of the breast, we investigated its role in kidney cancer. In renal cell carcinoma ELF5 expression was consistently decreased in tumor samples versus normal. ELF5 mRNA was decreased in 94% of lesions tested and ELF5 protein was undetectable in 40/40 kidney-derived carcinomas. Re-expression of the ELF5 gene in 786-O renal carcinoma cells suppressed their tumorigenic capacity in vitro and in vivo. This work is the first to suggest that ELF5 has tumor suppressor activity in the kidney.

Osaka University Center for Twin Research is currently organizing a government-funded, multidisciplinary research project using a large registry of aged twins living in Japan. The purpose of the project is to collect various information as well as biological resources from registered twins, and to establish a biobank and databases for preserving and managing these data and resources. The Center is collecting data from twin pairs, both of whom have agreed to participate in a one-day comprehensive medical examination. The following data are being collected: physical data (e.g., height, body mass, blood pressure, theoretical visceral fat, pulse wave velocity, and bone density), data regarding epidemiology (e.g., medical history, lifestyle, quality of life, mood status, cognitive function, and nutrition), electrocardiogram, ultrasonography (carotid artery and thyroid), dentistry, plastic surgery, positron emission tomography, magnetoencephalogram, and magnetic resonance imaging of brain. These data are then aggregated and systematically stored in specific databases. In addition, peripheral blood is obtained from the participants, and then genomic DNA is purified and sera are stored. A wide variety of studies are ongoing, and more are in the planning stage.

The contribution of genetic and environmental factors to the stability of obsessive–compulsive (OC) symptoms has not yet been established in adult population based samples. We obtained the Young Adult Self Report Obsessive–Compulsive Subscale in mono- and dizygotic twins from the population-based Netherlands Twin Register in 1991, 1995 and 1997 and the Padua Inventory Revised Abbreviated in 2002. Stability of OC symptoms was analyzed as a function of genetic and environmental components. Heritability of OC behavior was around 40% at each time-point, independent of the instrument used. OC behavior was moderately stable with correlations ranging between r = .2 (for 11-year intervals), .4 (for 4–5 year intervals) and .6 (for 2 year intervals). Genetic correlations across time were higher, varying between .4 and .9, indicating that the stability of OC symptoms is mainly due to stable genetic factors. This study showed a moderate heritability and stability for OC behavior in adults. Genetic stability across time is high.

Central body fat distribution has been shown to be related to hyperinsulinemia, insulin resistance, hypertriglyceridemia, and atherosclerosis to a greater degree than general obesity. There are known to be both genetic and environmental effects on all components of this clustering. Whether these genetic effects are due to one set of genes in common to the components or whether genetic influences on insulin resistance and/or general/abdominal fatness ‘turn on’ other genes that affect other components of the syndrome is not clear. We analyzed data from the Swedish Adoption/Twin Study of Aging (60% female; monozygotic = 116, dizygotic = 202; average age 65 years) to determine whether there were genetic and/or environmental factors shared among general body fat distribution, abdominal body fat distribution, fasting insulin levels and cardiovascular disease. We found additive genetic effects in males to be significantly different from those in females with genetic effects accounting for variance in waist–hip ratio (males = 28%; females = 49%), body mass index (males = 58%; females = 73%), fasting insulin levels (FI) (males = 27%; females = 49%), and cardiovascular disease (CVD) (males = 18%; females = 37%). There were also shared genetic and environmental effects among all the variables except CVD, but a majority of the genetic variance for these measures was trait specific. Twin Research (2000) 3, 43–50.

Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (rg = 0.16, p = 0.005) and environmental (re = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.

Over the past decade, epigenetic analyses have made important contributions to our understanding of healthy development and a wide variety of adverse conditions such as cancer and psychopathology. There is increasing evidence that DNA methylation is a mechanism by which environmental factors influence gene transcription and, ultimately, phenotype. However, differentiating the effects of the environment from those of genetics on DNA methylation profiles remains a significant challenge. Monozygotic (MZ) twin study designs are unique in their ability to control for genetic differences because each pair of MZ twins shares essentially the same genetic sequence with the exception of a small number of de novo mutations and copy number variations. Thus, differences within twin pairs in gene expression and phenotype, including behavior, can be attributed in the majority of cases to environmental effects rather than genetic influence. In this article, we review the literature showing how MZ twin designs can be used to study basic epigenetic principles, contributing to understanding the role of early in utero and postnatal environmental factors on the development of psychopathology. We also highlight the importance of initiating longitudinal and experimental studies with MZ twins during pregnancy. This approach is especially important to identify: (1) critical time periods during which the early environment can impact brain and mental health development, and (2) the specific mechanisms through which early environmental effects may be mediated. These studies may inform the optimum timing and design for early preventive interventions aimed at reducing risk for psychopathology.

Monochorionic dizygous twins are probably more frequent than considered previously as many cases remain unrecognized, especially when the children have the same sex. Here we present a pair of dizygous, sex-discordant monochorionic twins who were conceived after artificial insemination. Histological examination of the placenta and extensive genetic studies of the healthy boy and girl clearly proved that they indeed were monochorionic dizygous twins with a fully joined blood circulation. We conclude that when counseling parents expecting monochorionic twins of discordant sex, not only a disorder of sexual differentiation in one of the twins should be addressed but also the possibility of dizygosity with a completely normal (sexual) development of both children.

We used structural equation modeling to test the hypothesis that a General Factor of Personality (GFP) occupies the apex of the hierarchy of personality disorders in three validation samples of the Dimensional Assessment of Personality Pathology — Basic Questionnaire (DAPP-BQ). In a general population sample (N = 942), we found a GFP explained 34% of the variance in four first-order factors and 33% of the variance in all 18 scales. In a twin sample (N = 1,346), a GFP explained 35% of the variance in four first-order factors and 34% of the variance in all 18 scales. In a clinical sample (N = 656), a GFP explained 34% of the variance in four first-order factors and 30% of the variance in all 18 scales.

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.

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.

The relationship between subjective wellbeing (SWB) and self-reported sleep problems was investigated in a cohort of Norwegian twins aged 18 to 31 years. Questionnaire data from 8045 same- and opposite-sex twins were analyzed using structural equation modeling to explore the relative effects of genetic and environmental influences on phenotypic variance and covariance. Special attention was paid to sex-specific effects. The correlation between the phenotypes was estimated to be −.43. Univariate analyses indicated considerable genetic influences for both SWB and sleep problems, for male and female twins alike. The best fitting bivariate model specified additive genetic and individual environmental factors for both phenotypes, and nonadditive genetic effects for sleep problems, with no sex-specific effects. Genetic and environmental effects accounted for 60% and 40% of the phenotypic correlation, respectively. Additive genetic factors affecting the two phenotypes were correlated (−.85), suggesting that part of the genetic effects that positively influence SWB also protect against sleep problems. In conclusion, the results indicate considerable overlap in genetic etiology for SWB and sleep problems, for males and females alike.

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.

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.

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.

We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.

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.

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.

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.

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.