Twin studies have long provided a means to separate the contributions of genetic and environmental factors. A recent pioneering report by Baranzini et al. presented an analysis of the complete genomes and epigenomes of a monozygotic (MZ) twin pair discordant for multiple sclerosis. This failed to find any difference between the twins, raising doubts regarding the value of whole-genome twin studies for defining disease susceptibility alleles. However, the study was carried out with DNA extracted from blood. In many cases, the hematopoietic lineages of MZ twins are chimeric due to twin-to-twin exchange of hematopoietic stem cells during embryogenesis. We therefore wondered how chimerism might impact the ability to identify genetic differences. We inferred the blood chimerism rates and profiles of more than 30 discordant twin cases from a wide variety of medical conditions. We found that the genotype compositions of the twins were highly similar. We then benchmarked the performance of SNP callers to detect discordant variations using high-throughput sequencing data. Our analysis revealed that chimerism patterns, well within the range normally observed in MZ twins, greatly reduce the sensitivity of SNP calls. This raises questions regarding any conclusions of genomic homogeneity that might be drawn from studies of blood-derived twin DNA.

The present research examined the extent to which relations between social values and personality are due to shared genetic or environmental factors. Using the Rokeach (1973) Value Survey and a scoring key from Schwartz and Bilsky (1990), seven value scores (enjoyment, achievement, self-direction, maturity, prosocial, security, and restrictive conformity) were derived in a sample of twins. As expected, all of the value scales were found to have a significant genetic component, with values ranging from 36% for enjoyment to 63% for prosocial, and there were numerous significant phenotypic correlations found between the value scales and personality scores. Most important, bivariate genetic analyses revealed that some of these phenotypic correlations could be attributed to common genetic or environmental factors.

This study presents the first behavioral genetic investigation of the relationships between trait emotional intelligence (trait EI or trait emotional self-efficacy) and the Dark Triad traits of narcissism, Machiavellianism, and psychopathy. In line with trait EI theory, the construct correlated positively with narcissism, but negatively with the other two traits. Generally, the correlations were consistent across the 4 factors and 15 facets of the construct. Cholesky decomposition analysis revealed that the phenotypic associations were primarily due to correlated genetic factors and secondarily due to correlated nonshared environmental factors, with shared environmental factors being nonsignificant in all cases. Results are discussed from the perspective of trait EI theory with particular reference to the issue of adaptive value.

A twin item factor analytic model was developed to test for the presence of noninvariant age, sex, and age by sex interaction effects on the individual DSM-III-R criteria for major depression (MD). Based on 1-year reports, six of the nine MD criteria and duration requirement were found to have covariate factor loading and/or threshold effects that significantly deviated from their corresponding factor level expectations. A significant age effect was found for the binary duration variable factor loading. The ‘loss of interest’, ‘weight problems’ and ‘psychomotor problems’ criteria all displayed forms of threshold only effects. ‘Depressed mood’, ‘fatigue’, and ‘feeling worthless’ had more complex patterns that included both factor loading and threshold effects. A significant factor age by sex interaction effect indicating an increasing female mean difference with age was found to be largely associated with the presence of differential threshold covariate effects. Disagreement between estimated factor scores and DSM-derived affected vs. unaffected classification was ∼ 1.3%. Status on the duration requirement was found to be the one feature common to all discrepancies. The MD criteria set provided maximum information for calibrating MD factor scores in the scale region where discrepancies occurred. The dimensional modeling results are discussed in the broader context of epidemiological research and clinical assessment of major depression.

Aim: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. Methods: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. Results: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. Conclusion: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Our aim in this study is to describe the characteristics of sexual development in twins and estimate the role of heritability and environmental factors as causes of certain sexual disorders. Two hundred and ten adult same-sex twin pairs (92 monozygotic [MZ] female, 41 MZ male, 55 dizygotic [DZ] female and 22 DZ male pairs) were involved in the study. Data were collected in 1982 by self-administered questionnaires that included items on sexual maturation, sexual life, contraception, mutual sexual activity within twin pairs and alcohol use. The ratio of married to unmarried twins was nearly the same in MZs and DZs, with the exception that the divorce rate was higher in MZ female twins (14%), and DZ and male twins were slightly more likely to be single. Menarche was later in twins compared to non-twin Hungarian women. 57% of MZs experienced menarche within 3 months of each other, 77% within 6 months while it occurred for 30% and 43% respectively in DZs. The first seminal emission indicated some delay in male twins compared with the Hungarian general population sample. MZ first kisses occurred later than DZ's first kisses. The same was true for the first petting, masturbation and first sexual intercourse. Anorgasmy is 27% heritable but the estimate is not statistically significant. Concordance rate for premature ejaculation in MZs was greater than in DZs but the structural equation model showed significant misfit. Age at menarche appeared to be strongly heritable.

Postcoital psychological symptoms (PPS) is a virtually unexplored phenomenon in the female population even though women frequently complain about irritability and motiveless crying after intercourse and/or orgasm. The aim of this study was to explore the epidemiology and genetic influences of PPS in a UK population sample of women. 1,489 unselected female twins aged 18–85 completed questions on recent and persistent PPS and potential risk factors. Standard methods of quantitative genetic analysis were used to model latent genetic and environmental factors influencing variation in PPS. For identification of potential risk factors, regression analyses were conducted. Phenotypic variation in PPS was explored using a genetic variance component analysis (VCA) approach. We found 3.7% of women reported suffering from recent PPS and 7.7% from persistent PPS. Relationship satisfaction and experience of abuse were found to be independently associated with recent (OR 4.5, 95% CI 4.13–4.87 and OR 1.3, 95% CI 1.02–1.34, respectively) and persistent PPS (OR 2.53, 95% CI 2.17–2.81 and OR 1.16, 95% CI 1.09–1.26, respectively). VCA revealed that phenotypic variance was best explained by an additive genetic (AE) model, ascribing 28% (for recent PPS) and 26% (for persistent PPS) of phenotypic variance to additive genetic effects, with the rest being a result of individual experiences and random measurement error. To our knowledge, this is the first and largest study investigating the epidemiology of PPS. It seems that the most important targets for intervention and prevention occur outside of the family, such as relationship quality and satisfaction, and history of abuse.

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.

The present study is the first to examine relationships between alexithymia and trait emotional intelligence (trait EI or trait emotional self-efficacy) at the phenotypic, genetic, and environmental levels. The study was also conducted to resolve inconsistencies in previous twin studies that have provided estimates of the extent to which genetic and environmental factors contribute to individual differences in alexithymia. Participants were 216 monozygotic and 45 dizygotic same-sex twin pairs who completed the Toronto Alexithymia Scale-20. In a pilot study, a sub-sample of 118 MZ and 27 DZ pairs also completed the Trait Emotional Intelligence Questionnaire. Results demonstrated that a combination of genetic and non-shared environmental influences contribute to individual differences in alexithymia. As expected, alexithymia and trait EI were negatively correlated at the phenotypic level. Bivariate behavioral genetic analyses showed that that all but one of these correlations was primarily attributable to correlated genetic factors and secondarily to correlated non-shared environmental factors.

Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65–1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

An evolving hypothesis postulates that melanomas may arise through ‘nevus-associated’ and ‘chronic sun exposure’ pathways. We explored this hypothesis by examining associations between nevus-associated loci and melanoma risk across strata of body site and histological subtype. We genotyped 1028 invasive case patients and 1469 controls for variants in methylthioadenosine phosphorylase (MTAP), phospholipase A2, group VI (PLA2G6), and Interferon regulatory factor 4 (IRF4), and compared allelic frequencies globally and by anatomical site and histological subtype of melanoma. Odds-ratios (ORs) and 95% confidence intervals (CIs) were calculated using classical and multinomial logistic regression models. Among controls, MTAP rs10757257, PLA2G6 rs132985 and IRF4 rs12203592 were the variants most significantly associated with number of nevi. In adjusted models, a significant association was found between MTAP rs10757257 and overall melanoma risk (OR = 1.32, 95% CI = 1.14–1.53), with no evidence of heterogeneity across sites (Phomogeneity =.52). In contrast, MTAP rs10757257 was associated with superficial spreading/nodular melanoma (OR = 1.34, 95% CI = 1.15– 1.57), but not with lentigo maligna melanoma (OR = 0.79, 95% CI = 0.46–1.35) (Phomogeneity =.06), the subtype associated with chronic sun exposure. Melanoma was significantly inversely associated with rs12203592 in children (OR = 0.35, 95% CI = 0.16–0.77) and adolescents (OR = 0.61, 95% CI = 0.42–0.91), but not in adults (Phomogeneity =.0008). Our results suggest that the relationship between MTAP and melanoma is subtype-specific, and that the association between IRF4 and melanoma is more evident for cases with a younger age at onset. These findings lend some support to the ‘divergent pathways’ hypothesis and may provide at least one candidate gene underlying this model. Further studies are warranted to confirm these findings and improve our understanding of these relationships.

We report a 9-year-old girl with 3 Mb interstitial deletion of chromosome 15q24 identified by oligonucleotide array comparative hybridization. She is of Chinese ancestry and shared some typical features of previously reported 15q24 deletion cases such as mild dysmorphism with developmental and speech delay. She also had mild hearing loss that was reported in one other case. We compared all 19 cases that are identified from array-CGH. The deletion occurred within an 8.3 Mb region from 15q23 to 15q24.3. The minimum overlapping deleted region is less than 0.5 Mb from 72.3 Mb to 72.7 Mb. The functions of the nine annotated genes within the region and how they might contribute to the microdeletion phenotype are discussed.

Background: Somatic symptoms often co-occur with psychological symptoms but this overlap is poorly understood. Some aspects of this overlap differ in the South Asian context, but it is not clear whether this is a reporting effect or an underlying difference in experienced illness. Methods: Home interviews were administered to 4,024 twins randomly selected from a population-based twin register in the Colombo district of Sri Lanka (the CoTASS study). These included assessments of psychological, somatic and fatigue symptoms. The data were analyzed using factor analytic and quantitative genetic approaches. Results: Confirmatory factor analysis showed that the symptoms from the three scales represented three separate dimensions, rather than all tapping into a single dimension. However, familial correlations among the data were most consistent with a common pathway model. This implies that a portion of the underlying vulnerability is common across psychological, fatigue and somatic symptoms. There were sex differences in the etiology of this model, with shared environmental and genetic influences playing different roles in men and women. Conclusions: There is a complex etiological relationship between psychological, fatigue and somatic symptoms. This is similar in Sri Lanka to Western countries, but there may be a greater influence from the family environment, suggesting that care needs to be taken when generalizing research findings between countries. People who complain of certain fatigue or somatic symptoms may well also have psychological symptoms, or may have genetic or environmental vulnerabilities to such problems.

Mental health is increasingly defined not only by the absence of illness but by the presence of subjective well-being (SWB). Previous cohort studies have consistently shown that indicators of SWB predict favorable life outcomes, including better mental and somatic health, and longevity. The favorable effects associated with SWB have prompted new research aimed at raising happiness and wellbeing through individual interventions and public health initiatives. Standard observational studies of individual-level associations, however, are subject to potential confounding of exposure and outcome by shared genes and environment. The present study explored the association between SWB and increased longevity, using twin pair analyses to determine whether the association is consistent with causality or is due to genetic or environmental confounding. The study sample of 3,966 twins aged 70 or older, followed for a median time period of 9 years, was drawn from the population-based Longitudinal Study of Aging Danish Twins (LSADT). The association between SWB, operationalized as affect and life satisfaction, and all-cause mortality risk was examined using between-individual and within-pair survival analyses. As expected, at the individual level, SWB predicted increased longevity. Exposure effects were also present in unadjusted and adjusted within-pair analyses of 400 dizygotic (DZ) pairs and 274 monozygotic (MZ) pairs, indicating that SWB is associated with increased longevity independent of familial factors of genes and shared environment.

We analyzed the association between mean height and old age cognition in two Nordic twin cohorts with different childhood living conditions. The cognitive performance of 4720 twin individuals from Denmark (mean age 81.6 years, SD = 4.59) and Finland (mean age 74.4 years, SD = 5.26) was measured using validated cognitive screens. Taller height was associated with better cognitive performance in Finland (β-estimates 0.18 SD/10cm, p value < .001, for men and 0.13 SD, p = .008, for women), but this association was not significant in Denmark (β-estimates 0.0093 SD, p value = .16, for men and 0.0075 SD, p value = .016, for women) when adjusted for age and education/social class. Among Finnish participants higher variability of cognitive performance within shorter height quintiles was observed. Analysis using gene-environment interaction models showed that environmental factors exerted a greater impact on cognitive performance in shorter participants, whereas in taller participants' it was explained mainly by genetic factors. Our results suggest that shorter participants with childhood adversity are more vulnerable to environmental risk factors for cognitive impairment.

Few studies have examined differences of civil status of twins and singletons and the conclusions are contradictory. In the present study, based on a linkage between the Danish Twin Register, a random 5% sample of the total Danish population, and administrative register databases, the authors compare rates of marriage and divorce in a sample of 35,975 twins and 81,803 singletons born 1940–1964. Cox-regressions are used in order to control for potential confounders. We find that compared with singletons twins have significantly lower marriage rates: (males: 15–19 years: Hazard Ratio (HR) = 0.66 (95%CI: 0.58–0.76); 20–24 years: 0.85 (0.82–0.88); 25 years or more: 0.96 (0.93–0.98) and females: 15–19 years: 0.70 (0.67–0.75); 20–24 years: 0.83 (0.80–0.85); 25 years or more: 0.94 (0.91–0.97)). There is no difference in divorce rates for males, but a significantly lower divorce rate for female twins compared with singletons (HR=0.87, 95%CI: 0.83–0.90). These differences offset each other, thus 57% of both populations remain in their first marriage until censoring. The interpretation may be that since twins have a partner from birth, they do not have the same need for marriage as singletons but have more experience in maintaining a relationship if they do marry.

Self-report scales for symptoms of anxiety and depression are frequently used for screening and research purposes. A moderate phenotypic association between disorders measured by diagnostic interviews and symptoms of anxiety and depression measured by self-report scales has been shown, but little is known about the overlap in these phenotypes' genetic and environmental variance. In the present study, we used twin modeling to identify common genetic and environmental liabilities underlying the phenotypic association between the self-report Symptom Checklist-5 (SCL-5) and lifetime internalizing disorders derived from the Composite International Diagnostic Interview (CIDI). The sample consisted of 7,992 young adult twins from the Norwegian Institute of Public Health Twin Panel (NIPHT), who all responded to a questionnaire. A subset of 2,793 individuals later underwent structured interviews. The best fitting model showed a strong genetic correlation of 0.82 (95% confidence interval; 0.61–1.0) between current self-report symptoms of anxiety and depression, and lifetime internalizing disorders, which suggests an almost complete overlap in genetic liability. The correlation between environmental factors was much lower: 0.16 (0.00–0.34, 95% CI). This implies that brief self-report scales capture genetic variance that is highly overlapping with the genetic variance common to internalizing disorder diagnoses. It thus follows that SCL-5 and similar instruments may be used as screening instruments for genetic risk factors that influence liability to internalizing disorders. In addition, existing data on self-report symptoms of anxiety and depression can be used with increased confidence to specify models including effects from genes coding for internalizing disorders.

Background: We performed a genome-wide scan in a homogeneous Arab population to identify genomic regions linked to blood pressure (BP) and its intermediate phenotypes during mental and physical stress tests. Methods: The Oman Family Study subjects (N = 1277) were recruited from five extended families of ~10 generations. Hemodynamic phenotypes were computed from beat-to-beat BP, electrocardiography and impedance cardiography. Multi-point linkage was performed for resting, mental (word conflict test, WCT) and cold pressor (CPT) stress and their reactivity scores (s), using variance components decomposition-based methods implemented in SOLAR. Results: Genome-wide scans for BP phenotypes identified quantitative trait loci (QTLs) with significant evidence of linkage on chromosomes 1 and 12 for WCT-linked cardiac output (LOD = 3.1) and systolic BP (LOD = 3.5). Evidence for suggestive linkage for WCT was found on chromosomes 3, 17 and 1 for heart rate (LOD = 2.3), DBP (LOD = 2.4) and left ventricular ejection time (LVET), respectively. For △WCT, suggestive QTLs were detected for CO on chr11 (LOD = 2.5), LVET on chr3 (LOD = 2.0) and EDI on chr9 (LOD = 2.1). For CPT, suggestive QTLs for HR and LVET shared the same region on chr22 (LOD 2.3 and 2.8, respectively) and on chr9 (LOD = 2.3) for SBP, chr7 (LOD = 2.4) for SV and chr19 (LOD = 2.6) for CO. For △CPT, CO and TPR top signals were detected on chr15 and 10 (LOD; 2.40, 2.08) respectively. Conclusion: Mental stress revealed the largest number of significant and suggestive loci for normal BP reported to date. The study of BP and its intermediate phenotypes under mental and physical stress may help reveal the genes involved in the pathogenesis of essential hypertension.

The Dark Triad of personality, comprising Machiavellianism, narcissism, and psychopathy, was investigated in relation to the Supernumerary Personality Inventory (SPI) traits, because both sets of variables are predominantly distinct from the Big Five model of personality. Correlational and principal factor analyses were conducted to assess the relations between the Dark Triad and SPI traits. Multivariate behavioral genetic model-fitting analyses were also conducted to determine the correlated genetic and/or environmental underpinnings of the observed phenotypic correlations. Participants were 358 monozygotic and 98 same-sex dizygotic adult twin pairs from North America. As predicted, results revealed significant correlations between the Dark Triad and most SPI traits, and these correlations were primarily attributable to common genetic and non-shared environmental factors, except in the case of Machiavellianism, where shared environmental effects emerged. Three correlated factors were extracted during joint factor analysis of the Dark Triad and SPI traits, as well as a heritable general factor of personality — results that clarified the structure of the Dark Triad construct. It is concluded that the Dark Triad represents an exploitative and antisocial construct that extends beyond the Big Five model and shares a theoretical space with the SPI traits.

We aimed to determine (1) the prevalence of premenstrual syndrome in a sample of twins and (2) the relative contribution of genes and environment in premenstrual syndrome. A group of 193 subjects inclusive of same gender twins (n = 176) and females from opposite sex twin sets (n = 17) entered the study. Heritability analysis used same gender twin data only. The probandwise concordance rate for the presence or absence of premenstrual syndrome was calculated and the heritability of premenstrual syndrome was assessed by a quantitative genetic model fitting approach using MX software. The prevalence of premenstrual syndrome was 43.0% and 46.8% in monozygotic and dizygotic twins, respectively. The probandwise concordance for premenstrual syndrome was higher in monozygotic (0.81) than in dizygotic twins (0.67), indicating a strong genetic effect. Quantitative genetic modeling found that a model comprising of additive genetic (A) and unique environment (E) factors provided the best fit (A: 95%, E: 5%). No association was found between premenstrual symptom and the following variables: belonging to the opposite gender twin set, birth weight, being breast fed and vaccination. These results established a clear genetic influence in premenstrual syndrome.