We report on a 3-year-old girl, from a 3-generation family with an FGFR3 Pro250Arg mutation, who in addition to craniosynostosis, had a laterality disorder and hepatoblastoma, following a pregnancy complicated by maternal insulin-dependent diabetes. The clinical features possibly result from the combined effects of the maternal diabetes and the familial FGFR3 mutation, thus representing a unique gene–environment interaction that may have implications for the understanding of the phenotypes described in this child.

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.

Specific environments and social relationships may alter the impact of genes. Previous studies have shown marriage to moderate heritability for depressive symptoms in females, suggesting that marriage provides protection or compensation against genetic risks. Similar mechanisms may be relevant for subjective wellbeing (SWB), which is considerably influenced by genes and almost universally associated with marital status. Questionnaire data on SWB from a population-based sample of 1250 monozygotic (MZ) and 981 dizygotic (DZ) male and female twin pairs (n = 4462) were analyzed using structural equation modeling by means of Mx to investigate genetic and environmental influences on SWB across marital status. Resemblance for SWB in MZ twins exceeded that of DZ twins, but the magnitude of this difference varied across marital status. Genetic factors explained 51% and 54% of the variance in SWB among unmarried males and females, and 41% and 39% in married or cohabitating respondents. Remaining variance was attributable to the nonshared environment. The genetic influences were partly different (rg = 0.64) across marital status in females, but overlapping in married and single males. Our findings show that marriage moderates the magnitude of genetic influences on SWB in both males and females, with a smaller estimate of genetic influences for those with a marital or equivalent partner. The genetic influences on SWB are thus clearly contingent on the environmental context.

Optimism has a positive influence on mental and somatic health throughout lifetime and into old age. This association is mainly due to shared genetic influences, with some indication of sex differences in the heritability of these and related traits (e.g., depression and subjective wellbeing). Here we extend our initial study of Australian twins by combining with data available from Swedish twins, in order to increase the power to explore potential sex differences in the genetic architecture of optimism, mental and self-rated health and their covariation. Optimism, mental, and self-rated health were measured in 3053 Australian (501 identical female (MZf), 153 identical male (MZm), 274 non-identical female (DZf), 77 non-identical male (DZm), and 242 non-identical opposite-sex twin pairs, and 561 single twins; mean age 60.97 ± 8.76), and 812 Swedish (71 MZf, 53 MZm, 93 DZf and 67 DZm twin pairs, and 244 single twins; mean age 60 ± 14.3) twin individuals using the Life Orientation Test (LOT), the General Health Questionnaire (GHQ) and a single-item self-rating of overall health, respectively. In females all three traits were moderately heritable (.27–.47), whereas in males heritability was substantially lower (.08–.19), but genetic modeling showed that sex differences were not significant. The absence of significant sex differences, despite the consistent trend across the two cohorts, is likely due to a lack of power, raising the importance for future studies, on the same or similar traits, to utilize large samples and to keep the possibility of sex differences in mind when conducting their analyses.

This study employs multiple regression models based on DeFries and Fulker (1985), and a large sample of twins, to assess heritability in attitudes towards economic risk, and the extent to which this heritability differs between males and females. Consistent with Cesarini et al. (2009), it is found that attitudes towards risk are moderately heritable, with about 20 percent of the variation in these attitudes across individuals being linked to genetic differences. This value is less than one-half the estimates reported by Zyphur et al. (2009) and Zhong et al. (2009). While females are more risk averse than males, there is no evidence that heritability in attitudes towards risk differs between males and females. Even though heritability is shown to be important to economic risk-taking, the analyses suggest that multivariate studies of the determinants of attitudes towards risk which to not take heritability into consideration still provide reliable estimates of the partial effects of other key variables, such as gender and educational attainment.

The purpose of this study was to examine potential biases in family history reports of problem gambling and gambling frequency. Same-sex twin pairs discordant for a history of problem (n = 230 pairs) and pathological gambling (n = 48 pairs) and for three indexes of gambling frequency (ever gambling, monthly gambling, and weekly gambling; n = 44–517 pairs) were identified from a large Australian national twin study. The problem gambling affected twin was significantly more likely to endorse paternal problem gambling than the problem gambling unaffected cotwin (OR = 5.5), and similar findings were obtained for family history reports of gambling frequency (OR = 2.0–2.8). These results could not be explained by differences between the discordant pairs in whether they had spent time gambling with the parents; there was no association between a history of problem, monthly or weekly gambling and having gambled with the parents among discordant twin pairs. The results of this study suggest that relying solely on family history assessments of disordered gambling and gambling involvement can lead to incorrect estimates of the strength of the family history effect.

The aim of this study is to characterize the relationship between major depression and the metabolic syndrome in a large community based sample of Australian men and women aged 26–90 years. A lifetime history of major depression was assessed by telephone interview following the DSM–III-R. A current history of metabolic syndrome was assessed following the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP AP-III) guidelines 1 to 3 years later. Logistic regression was used to estimate the association between depression and the metabolic syndrome, and its component criteria, controlling for age, sex and alcohol dependence. There was no association between a lifetime history of major depression and the presence of the metabolic syndrome. There was a weak association between depression and low high-density lipoprotein cholesterol but not with other component criteria of the metabolic syndrome. Despite calls for interventions directed at depression to reduce the onset of the metabolic syndrome there are important failures to replicate in large samples such as this, no consensus regarding the threshold at which depression may pose a significant risk even allowing for heterogeneity across populations, and no consensus regarding confounders that may explain inter-study differences. The absence of any dosage effect of depression on the associated risk for the metabolic syndrome in other unselected samples does not support a direct causal relationship. The call for intervention studies on the basis of the currently published evidence base is unwarranted.

We examined the variation and heritability of DSM-IV nicotine withdrawal (NW) in adult and adolescent male and female twin cigarette smokers (who reported smoking 100 or more cigarettes lifetime). Telephone diagnostic interviews were completed with 3,112 Australian adult male and female smokers (53% women; age: 24–36) and 702 Missouri adolescent male and female smokers (59% girls; age: 15–21). No gender or cohort differences emerged in rates of meeting criteria for NW (44%). Latent class analyses found that NW symptoms were best conceptualized as a severity continuum (three levels in adults and two levels in adolescents). Across all groups, increasing NW severity was associated with difficulty quitting, impairment following cessation, heavy smoking, depression, anxiety, conduct disorder and problems with alcohol use. NW was also associated with seeking smoking cessation treatment and with smoking persistence in adults. The latent class structure of NW was equally heritable across adult and adolescent smokers with additive genetic influences accounting for 49% of the variance and the remaining 51% of variance accounted for by unique environmental influences. Overall, findings suggest remarkable similarity in the pattern and heritability of NW across adult and adolescent smokers, and highlight the important role of NW in psychiatric comorbidity and the process of smoking cessation across both age groups.

We assessed the heritability of head circumference, an approximation of brain size, in twin-sib families of different ages. Data from the youngest participants were collected a few weeks after birth and from the oldest participants around age 50 years. In nearly all age groups the largest part of the variation in head circumference was explained by genetic differences. Heritability estimates were 90% in young infants (4 to 5 months), 85–88% in early childhood, 83–87% in adolescence, 75% in young and mid adulthood. In infants younger than 3 months, heritability was very low or absent. Quantitative sex differences in heritability were observed in 15- and 18-year-olds, but there was no evidence for qualitative sex differences, that is, the same genes were expressed in both males and females. Longitudinal analysis of the data between 5, 7, and 18 years of age showed high genetic stability (.78 > RG > .98). These results indicate that head circumference is a highly heritable biometric trait and a valid target for future GWA studies.

Fellman and Eriksson (2010) cited my suggestion that the sex ratio (proportion male) of monozygotic (MZ) twins is lower than that of dizygotic (DZ) twins (James 1975). Here I offer elaborations on and potential explanations for this.

It has been assumed that sexual activity during pregnancy would lead to an increased risk for miscarriage and other complications of pregnancy. Various studies showed no association of sexual behavior and pregnancy complications in single pregnancies. The aim of our study was to evaluate changes in sexual activity in women with twin pregnancies and whether a higher frequency of sexual intercourse was associated with an increased risk for pregnancy complications. We report on 50 women with twin pregnancies who answered a questionnaire on sexual behavior during pregnancy. At the time of delivery, patients were aged 31.0 ± 4.8 years. All women reported to have had sexual intercourse during pregnancy. In contrast to the first trimester in the vast majority of patients (41/50, 82.0%) the coital frequency decreased in the last month of pregnancy. Patients who had become pregnant after in-vitro fertilization were significantly less likely to have regular sexual intercourse than patients after spontaneous conception during early pregnancy (p = .002). No statistical significances were found when the rates of preterm delivery before the 37th gestational week were compared to the frequencies of sexual intercourse during early pregnancy and during late pregnancy (p >.05). In conclusion, our study demonstrates a decrease in frequency of sexual intercourse from early to late pregnancy in the specific collective of women with twin pregnancies, especially in women after in-vitro fertilization. There was no association between sexual activity and preterm delivery.

Twins achieved through in-vitro fertilisation often undergo a viability ultrasound at 6–9 weeks of gestation. The presence of inter-twin crown-rump length discordance at this stage is not an uncommon finding; however the clinical significance of this is unknown. We analyzed 218 dichorionic twin pregnancies, producing two live fetuses > 24 weeks gestation, to determine whether inter-twin discordance (≥ 85th centile) in the mid-first trimester was associated with birthweight discordance (> 20%), or small for gestational age (< 10th centile). The incidence of birthweight discordance and small for gestational age infants were determined, with no increased risk found for the discordant population. This may provide some reassurance to treating clinicians.

Objective: To evaluate the influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies. Methods: 200 twin pregnancies were included in the study. 157 nondiabetic pregnant women with twin gestations and 43 twin pregnancies with gestational diabetes mellitus (GDM) with viable fetuses born after 24 weeks of gestation were enrolled. Influence of maternal age, body-mass-index at the time of the oral glucose tolerance test, parity, smoking, chorionicity, gestational age at delivery and diagnosis of GDM on weight discrepancy of the twins was evaluated. Results: Mean weight discrepancy of all analyzed twin pregnancies was 285 grams (± 231), relative weight discrepancy was 11.3% (± 8.6). Univariate regression analyses showed that GDM, chorionicity and gestational age at delivery were significantly associated with weight discrepancy. In the multivariate model only diagnosis of GDM was significantly associated with weight discrepancy. Conclusion: Twin pregnancies with insulin requiring gestational diabetes seem to have less birth weight discrepancy than twin pregnancies with normal glucose tolerance.

Self-rated health questions have been proven to be a highly reliable and valid measure of overall health as measured by other indicators in many population groups. It also has been shown to be a very good predictor of mortality, chronic or severe diseases, and the need for services, and is positively correlated with clinical assessments. Genetic factors have been estimated to account for 25–64% of the variance in the liability of self-rated health. The aim of the present study was to identify Single Nucleotide Polymorphisms (SNPs) underlying the heritability of self-rated health by conducting a genome-wide association analysis in a large sample of 6,706 Australian individuals aged 18–92. No genome wide significant SNPs associated with self-rated health could be identified, indicating that self-rated health may be influenced by a large number of SNPs with very small effect size. A very large sample will be needed to identify these SNPs.