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Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.
Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent (‘phoria’) and manifest (‘tropia’) strabismus using cover–uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50–0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.
Cannabis is the most widely used illicit drug throughout the developed world and there is consistent evidence of heritable influences on multiple stages of cannabis involvement including initiation of use and abuse/dependence. In this paper, we describe the methodology and preliminary results of a large-scale interview study of 3,824 young adult twins (born 1972–1979) and their siblings. Cannabis use was common with 75.2% of males and 64.7% of females reporting some lifetime use of cannabis while 24.5% of males and 11.8% of females reported meeting criteria for DSM-IV cannabis abuse or dependence. Rates of other drug use disorders and common psychiatric conditions were highly correlated with extent of cannabis involvement and there was consistent evidence of heritable influences across a range of cannabis phenotypes including early (≤15 years) opportunity to use (h2 = 72%), early (≤16 years) onset use (h2 = 80%), using cannabis 11+ times lifetime (h2 = 76%), and DSM abuse/dependence (h2 = 72%). Early age of onset of cannabis use was strongly associated with increased rates of subsequent use of other illicit drugs and with illicit drug abuse/dependence; further analyses indicating that some component of this association may have been mediated by increasing exposure to and opportunity to use other illicit drugs.
Previous studies of risk factors for sickness absence (SA) focus primarily on psychosocial and work environmental exposures. The aim of this study was to investigate the relative contribution of genetic influences on SA among women and men. The population-based study sample of Swedish twins (34,547) included 13,743 twin pairs of known zygosity, 3,495 monozygotic, 5,073 same-sexed dizygotic, and 5,175 opposite sexed. The point prevalence of long-term SA (≥15 days) in each zygosity and sex group was calculated. The risk of SA was estimated as an odds ratio (OR) with 95% confidence intervals (CI) where the odds for twins on SA to have a co-twin on SA was compared to the OR for SA in twins whose co-twin were not sickness absent. Intrapair correlations and probandwise concordance rates were calculated and standard biometrical genetic model-fitting methods were used to estimate the heritability of SA. The prevalence of SA was 8.8% (women 10.7%; men 6.5%). Intrapair similarity was higher among monozygotic than dizygotic twin pairs. The best-fitting model showed no sex differences in genetic effects or variance components contributing to SA. The heritability estimate was 36% (95% CI: 35–40%). Results suggest genetic contribution to the variation of SA and that environmental factors have an important role, for women and men. As SA seem to be influenced by genetic factors, future studies of associations between risk factors and SA should consider this potentially confounding effect.
The aim was to determine the difference in intelligence between singletons and twins in young adulthood. Data from the Medical Birth Register of Norway were linked with register data from the Norwegian National Conscript Service. The study base consisted of data on the 445,463 males who were born alive in either single or twin births in Norway during 1967–1984 and who were examined at the time of the mandatory military conscription (age 18–20). Within this study base, there were data on 1,653 sibships of full brothers that included at least one man born in single birth and at least one man born in twin birth (4,307 persons, including 2,378 twins and 1,929 singletons). The intelligence scores of the singletons were 11% (95% confidence interval [CI]: 9–14%) of a standard deviation higher than those of the twins, after adjustment for birth year, birth order, parental ages at delivery, parental education levels, and other factors. The adjusted within-family difference was also 11% (95 % CI: 6–16%) of a standard deviation, indicating that unmeasured factors shared by siblings (e.g., maternal body height) have not influenced the estimate in important ways. When gestational age at birth was added to the model, the estimate for the difference in intelligence score was approximately the same. Including birth weight in the model strongly reduced the estimate. In conclusion, twins born in Norway during 1967–1984 had slightly lower intelligence in early adulthood compared with the singletons.
Objective: Posttraumatic stress disorder (PTSD) is one of the only disorders in the Diagnostic and Statistical Manual of Mental Disorders that requires an environmental exposure. The relationship between liability factors for trauma exposure and those for PTSD symptoms following exposure are unclear. Methods: Exposure to a trauma and resulting PTSD symptoms were assessed in a sample of 2,794 members of the Norwegian Institute of Public Health Twin Panel. Results: In the full sample, 737 twins experienced a trauma. A modified causal, contingent, common pathway model was used to examine trauma exposure and liability for PTSD. Genetic and common environmental factors could not be distinguished, so a model that included only familial and individual specific components was fit. The best-fitting model suggested that familial factors played an important role in liability for trauma exposure and for resulting PTSD symptoms, and that there was a modest transmission between trauma exposure and subsequent PTSD symptoms. Conclusions: One third of the variance in liability of PTSD symptoms is due to familial factors, and of this, approximately one fifth overlaps with the familial liability for trauma exposure while the other four fifths of the variance is specific to the risk of PTSD symptoms following exposure. The hypothesis that PTSD is etiologically similar to exposures to a traumatic event is not supported, suggesting that the factors that confer risk for trauma do not overlap completely with those that confer risk for PTSD.
The present study investigated the extent to which individual differences in humor styles are attributable to genetic and/or environmental factors in an Australian sample. Participants were 934 same-sex pairs of adult twins from the Australian Twin Registry (546 monozygotic pairs, 388 dizygotic pairs) who completed the Humor Styles Questionnaire (HSQ). The HSQ measures four distinct styles of humor — affiliative, self-enhancing, aggressive, and self-defeating. Results revealed that additive genetic and non-shared environmental factors accounted for the variance in all four humor styles, thus replicating results previously obtained in a sample of twins from the United Kingdom. However, a study conducted with a U.S. sample produced different results and we interpret these findings in terms of cross-cultural differences in humor.
The mothers of 603 pairs of 3- to 13-year-old twins in Korea completed the Emotionality, Activity, Sociability (EAS) Temperament Survey and the Strengths and Difficulties Questionnaire in reference to their twins. Principal factor analysis of the seven scales comprising these measures yielded a general factor on which all the scales had moderate to large loadings. Univariate behavioral genetic analyses showed that individual differences on this general factor could best be accounted for by additive genetic and non-shared environmental effects, with a heritability of 53%. The results strengthen the construct validity of the general factor of personality (GFP) by extracting this higher-order dimension from disparate measures, and have implications regarding social desirability criticisms applied to the GFP theory.
We analyzed the characteristics associated with the growth in weight of Japanese triplets from birth to 12 years of age. The study included 376 mothers and their 1,128 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets’ weight growth, gestational age, sex, parity, maternal age at delivery, maternal height, and maternal body mass index were obtained from records in the Maternal and Child Health Handbooks and records in the school where children receive health check-ups. The weight deficit of the triplets compared to the general population of Japan remained between 10% and 17% until 12 years of age. Moreover, at 12 years of age, the differences of weight between the general population and triplets were approximately –4.75 kg for boys and –6.00 kg for girls. Very low birth weight had the strongest contribution to body weight until 8 years of age. After 8 years of age, maternal body mass index was a significant factor affecting the weight of triplets until 12 years of age.
This study was designed to evaluate the degree of placenta share discordance in relation to the betamethasone-induced return of positive end-diastolic flow in monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was defined as one twin having an estimated fetal weight below the 10th percentile combined with an estimated fetal weight discordance >25%. The umbilical artery Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the first dose of betamethasone administration was recorded. The estimated individual placental weight in monochorionic twins was obtained by cutting the placenta along the vascular equator into two territories; the placenta share discordance was calculated as [(estimated individual placental weight of appropriated for gestational age twin- estimated individual placental weight of growth restricted twin)/estimated individual placental weight of appropriated for gestational age twin] × 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced return of positive umbilical artery end-diastolic flow. The difference of placenta share discordance and birth weight discordance were not significantly different between twins with and without betamethasone-induced return of positive umbilical artery end-diastolic flow. Thus, according to our study results, it was proposed that although the placenta share discordance correlated with the abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the betamethasone-induced return of positive umbilical artery end-diastolic flow, however, did not reveal the similar relationship with the severity of placenta share discordance.
Selected highlights from the 14th International Congress on Twin Studies, set in Florence, Italy in April 2012, are presented. This meeting, which traditionally occurred every three years, is now being held every two years. Reviews of research on the topics of stress and aging (telomere erosion), the genetics of MZ twinning, developmental dysplasia, and fertility of mothers of twins follow. The final section includes several public interest items, namely an exhibit of twins' video portraits, unusual physical look-alikes, and young and adult twin television and film actors.