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We compare the power of two different approaches to detect passive genotype-environment (GE) covariance originating from cultural and genetic transmission operating simultaneously. In the traditional nuclear twin family (NTF) design, cultural transmission is estimated from the phenotypic covariance matrices of the mono- and dizygotic twins and their parents. Here, phenotyping is required in all family members. A more recent method is the transmitted-nontransmitted (T-NT) allele design, which exploits measured genetic variants in parents and offspring to test for effects of nontransmitted alleles from parents. This design requires two-generation genome-wide data and a powerful genome-wide association study (GWAS) for the phenotype in addition to phenotyping in offspring. We compared the power of both designs. Using exact data simulation, we demonstrate three points: how the power of the T-NT design depends on the predictive power of polygenic risk scores (PRSs); that when the NTF design can be applied, its power to detect cultural transmission and GE covariance is high relative to T-NT; and that, given effect sizes from contemporary GWAS, adding PRSs to the NTF design does not yield an appreciable increase in the power to detect cultural transmission. However, it may be difficult to collect phenotypes of parents and the possible importance of gene × age interaction, and secular generational effects can cause complications for many important phenotypes. The T-NT design avoids these complications. [ABSTRACT FROM AUTHOR]

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented. [ABSTRACT FROM AUTHOR]

Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable. [ABSTRACT FROM AUTHOR]

Work incapacity is a major public health challenge and an economic burden to both society and individuals. Understanding the underlying causes is becoming ever more relevant as many countries face an aging workforce. We examined stability and change in genetic and environmental factors influencing work incapacity from age 18 until retirement, and sex differences in these effects. The large population-based sample comprised information from 28,759 twins followed for up to 23 years combined with high-quality national registry data. We measured work incapacity as the total proportion of potential workdays lost due to sickness absence, rehabilitation and disability benefits. Structural equation modeling with twin data indicated moderate genetic influences on work incapacity throughout life in both men and women, with a high degree of genetic stability from young to old adulthood. Environmental influences were mainly age-specific. Our results indicate that largely the same genetic factors influence individual differences in work incapacity throughout young, middle and older adulthood, despite major differences in degree of work incapacity and probable underlying medical causes. [ABSTRACT FROM AUTHOR]

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 60,000 twins primarily born or living in Virginia, North Carolina and South Carolina. Researchers may utilize the MATR for administration of research services, including study recruitment, data or sample (e.g., DNA) collection, archival dataset creation, as well as data collection through mailed, phone or online surveys. In addition, the MATR houses the MATR Repository, with over 1700 DNA samples primarily from whole blood available for researchers interested in DNA genotyping. For over 40 years MATR twins have participated in research studies with investigators from a range of scientific disciplines and institutions. These studies, which have resulted in numerous publications, explored diverse topics, including substance use, smoking behaviors, developmental psychopathology, bullying, children's health, cardiovascular disease, cancer, the human microbiome, epigenetics of aging, children of twins and sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities. [ABSTRACT FROM AUTHOR]

Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5'UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism. [ABSTRACT FROM AUTHOR]

In 1968, long before the publication of Stephen J. Gould's The Mismeasure of Man, Herrnstein and Murray's The Bell Curve, or Arthur Jensen's Bias in Mental Testing, Irving Gottesman published a book chapter that addressed head-on the issues that would define the relationship between the genetics of social behavior and large-scale social theory for the next 50 years. That he could do so with his characteristic scholarly thoroughness and scientific tough-mindedness without once lapsing into regressive hereditarianism is a testimony to the scope of his scientific knowledge and the generosity of his intellectual spirit. [ABSTRACT FROM AUTHOR]

A discordant twin gestation, in which one fetus is significantly growth restricted, compared to the other normal twin, is a unique model that can be used to elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. In many model systems, placental transcription factor genes regulate fetal growth. Transcription factors regulate growth through their activation or repression of downstream target genes that mediate important cell functions. The objective of this study was to determine the expression of the placental HLX homeobox gene transcription factor and its downstream target genes in dizygotic twins with growth discordance. In this cross-sectional study, HLX and its downstream target genes' retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C) expression levels were determined in placentae obtained from dichorionic diamniotic twin pregnancies (n = 23) where one of the twins was growth restricted. Fetal growth restriction (FGR) was defined as small for gestational age with abnormal umbilical artery Doppler indices when compared with the normal control co-twin. Homeobox gene HLX expression was significantly decreased at both the mRNA and protein levels in FGR twin placentae compared with the normal control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were also significantly decreased and increased, respectively, at both the mRNA and protein levels in FGR twin placentae compared with normal control co-twin placentae (p < .05). Together, these observations suggest an important association between HLX transcription factor expression and abnormal human placental development in discordant twin pregnancies. [ABSTRACT FROM AUTHOR]

Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. Our aim was to determine which PD traits are linked phenotypically and genetically to cocaine use. Cross-sectional data were obtained in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins (µage = 28.2 years, range = 19-36) from the Norwegian Institute of Public Health Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to identify PDs related to cocaine use. Twin models were fitted to estimate genetic and environmental associations between the PD traits and cocaine use. In the multiple regression, antisocial (OR = 4.24, 95% CI [2.66, 6.86]) and borderline (OR = 2.19, 95% CI [1.35, 3.57]) PD traits were significant predictors of cocaine use. In the LASSO regression, antisocial, borderline, and histrionic were significant predictors of cocaine use. Antisocial and borderline PD traits each explained 72% and 25% of the total genetic risks in cocaine use, respectively. Genetic risks in histrionic PD were not significantly related to cocaine use. Importantly, after removing criteria referencing substance use, antisocial PD explained 65% of the total genetic variance in cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is the strongest correlate of cocaine use, for which the association is driven largely by common genetic risks. [ABSTRACT FROM AUTHOR]

Monozygotic (MZ) and dizygotic (DZ) twins participate in research that partitions variance in health, disease, and behavior into genetic and environmental components. However, there are other innovative roles for twins in medical research. One such way is involving MZ and/or DZ twins in co-twin control-designed randomized controlled trials (RCTs). To our knowledge, no reviews have been conducted that summarizes the involvement of twins in RCTs. Therefore, we conducted a systematic literature search using the U.S. Clinical Trials Database, NHS electronic databases, MEDLINE, EMBASE, and PsychINFO for RCTs on publications involving MZ and/or DZ twins as RCT participants. Out of the 186,027 clinical trials registered in the U.S. clinical trial register ClinicaTrails.gov, only six RCTs used twins as participants. From 1,598 articles identified in our search, 50 peer-reviewed English language publications met our pre-defined inclusion criteria. Sample sizes for RCTs have ranged from a total number of participants from 2 to 1,162; however, 32 (64%) studies had a sample size of 100 or less, and of those, 12 (24%) had fewer than 10. Both MZ and DZ twins have been recruited to the RCTs. In most instances (33/50) each twin from a pair were assigned to different study arms. Most of those studies included MZ twins only. Despite the methodological advantages, the use of MZ and DZ twins as participants in interventional RCTs appeared limited. The continuous development of innovative twin designs, especially RCTs, indicates that twin research can extend beyond the more widely recognized heritability estimates. [ABSTRACT FROM AUTHOR]

The genetic and environmental contributions of negative valence systems (NVS) to internalizing pathways study (also referred to as the Adolescent and Young Adult Twin Study) was designed to examine varying constructs of the NVS as they relate to the development of internalizing disorders from a genetically informed perspective. The goal of this study was to evaluate genetic and environmental contributions to potential psychiatric endophenotypes that contribute to internalizing psychopathology by studying adolescent and young adult twins longitudinally over a 2-year period. This report details the sample characteristics, study design, and methodology of this study. The first wave of data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2) is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166 monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated at time 1. Twin participants completed self-report surveys and participated in experimental paradigms to assess processes within the NVS. Additionally, parents completed surveys to report on themselves and their twin children. Findings from this study will help clarify the genetic and environmental influences of the NVS and their association with internalizing risk. The goal of this line of research is to develop methods for early internalizing disorder risk detection. [ABSTRACT FROM AUTHOR]

CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta. [ABSTRACT FROM AUTHOR]

BackgroundDSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known.MethodsWe use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors.ResultsWhen measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91.ConclusionThe pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs. [ABSTRACT FROM PUBLISHER]

Cryptorchidism represents one of the most common human congenital anomalies. In most cases, its etiology remains unclear and seems to be multifactorial. In the present study, a pair of monozygotic twins discordant for cryptorchidism was identified. Twin zygosity was confirmed by microsatellite genotyping. Whole exome sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) of DNA extract from leucocytes were performed to, respectively, evaluate their exomes and epigenomes. No differences in exome sequencing data were found between the twins after validation. MeDIP-Seq analysis detected 5,410 differentially hypermethylated genes and 2,383 differentially hypomethylated genes. Bioinformatic analysis showed that these genes belonged to several biological processes and signaling pathways, including regulation of actin cytoskeleton, which has been previously implicated in the etiology of cryptorchidism. The findings of the present study suggest that non-genetic factors might contribute to the pathogenesis of cryptorchidism. [ABSTRACT FROM PUBLISHER]

Background: The link between asthma and exhaled nitric oxide (FENO) is not completely understood. The aim of this study was to estimate the association between FENO and asthma, taking genetics, sensitization, and inhaled corticosteroids (ICS) into account.Methods: A total of 681 twins (53% monozygotic [MZ] and 47% dizygotic [DZ]) from the population-based STOPPA study (mean age 12.6 years) were recruited and information on FENO (parts per billion), parental report of current asthma, sensitization to airborne allergens (Phadiatop; IgE ≥0.35 kUA/l), and ICS-treatment was collected. We estimated the association between FENO and asthma, sensitization, and ICS in all twins and within pairs (DZ and MZ) to address shared genetic and environmental factors. Linear regression of log-transformed FENO was used and results presented as exponentiated regression coefficients (exp[β]), with 95% confidence interval (CI).Results: We found an association between asthma and FENO in all twins, exp(β) 1.31 [1.11, 1.54]. In within-pairs analysis, the association was stronger within DZ pairs discordant for FENO, exp(β) 1.50 [1.19, 1.89], compared to MZ pairs, exp(β) 1.07 [0.84, 1.37], p = .049. There was no difference in FENO in non-sensitized children with asthma, compared to children with neither asthma nor sensitization, exp(β) 0.89 [0.77, 1.03]. However, increased FENO was associated with sensitization, exp(β) 1.48 [1.30, 1.69], and with sensitization together with asthma, exp(β) 1.98 [1.57, 2.51], in all twins and within DZ pairs discordant for FENO, but not in MZ pairs. The FENO asthma association remained in DZ pairs without regular ICS-treatment.Conclusions: The association between FENO and asthma is explained by genetics and sensitization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

The aim of this study was to investigate the twinning rates (TWRs) in isolates relative to the TWRs in the surrounding populations. It is not uncommon that the TWR shows extreme values (high or low rates) within isolated subpopulations. Starting from the isolated populations of the Åland Islands in Finland (high rates), we enlarged our studies to other isolated subpopulations in other countries: the island of Gotland (high rates), the county of Älvsborg located in the southwestern part of Sweden (low rates), and mountain villages in Norway. In our statistical analyses, we paid special attention to the robustness of the variance formula of the TWR and to alternative confidence intervals for the TWR. Particularly, we show how to obtain the most precise confidence intervals for the twinning rates. These statistical methods are crucial when the extreme TWRs within subpopulations are compared with the TWRs within the general population. One must decide whether the differences are real or caused by random fluctuations within the small isolates. [ABSTRACT FROM PUBLISHER]

BackgroundMental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD).MethodA total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON.ResultsA statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD.ConclusionsThis is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology. [ABSTRACT FROM PUBLISHER]

The relationship between the genetic and environmental risk factors for alcohol use disorders (AUD) detected in Swedish medical, pharmacy, and criminal registries has not been hitherto examined. Prior twin studies have varied with regard to the detection of shared environmental effects and sex differences in the etiology of AUD. In this report, structural equation modeling in OpenMx was applied to (1) the three types of alcohol registration in a population-based sample of male–male twins and reared-together full and half siblings (total 208,810 pairs), and (2) AUD, as a single diagnosis, in male–male, female–female, and opposite-sex (OS) twins and reared-together full and half siblings (total 787,916 pairs). An independent pathway model fit best to the three forms of registration and indicated that between 70% and 92% of the genetic and 63% and 98% of the shared environmental effects were shared in common with the remainder unique to each form of AUD registration. Criminal registration had the largest proportion of unique genetic and environmental factors. The best fit model for AUD estimated the heritability to be 22% and 57%, respectively, in females and males. Both shared (12% vs. 6%) and special twin environment (29% vs. 2%) were substantially more important in females versus males. In conclusion, AUD ascertained from medical, pharmacy, and criminal Swedish registries largely share the same genetic and environmental risk factors. Large sex differences in the etiology of AUD were seen in this sample, with substantially stronger familial environmental and weaker genetic effects in females versus males. [ABSTRACT FROM PUBLISHER]

Investigations on the relationship between sweet taste perception and body mass index (BMI) have been inconclusive. Here, we report a longitudinal analysis using a genetically informative sample of 1,576 adolescent Australian twins to explore the relationship between BMI and sweet taste. First, we estimated the phenotypic correlations between perception scores for four different sweet compounds (glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame) and BMI. Then, we computed the association between adolescent taste perception and BMI in early adulthood (reported 9 years later). Finally, we used twin modeling and polygenic risk prediction analysis to investigate the genetic overlap between BMI and sweet taste perception. Our findings revealed that BMI in early adulthood was significantly associated with each of the sweet perception scores, with the strongest correlation observed in aspartame with r = 0.09 (p = .007). However, only limited evidence of association was observed between sweet taste perception and BMI that was measured at the same time (in adolescence), with the strongest evidence of association observed for glucose with a correlation coefficient of r = 0.06 (p = .029) and for aspartame with r = 0.06 (p = .035). We found a significant (p < .05) genetic correlation between glucose and NHDC perception and BMI. Our analyses suggest that sweet taste perception in adolescence can be a potential indicator of BMI in early adulthood. This association is further supported by evidence of genetic overlap between the traits, suggesting that some BMI genes may be acting through biological pathways of taste perception. [ABSTRACT FROM AUTHOR]

Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism (r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables. [ABSTRACT FROM PUBLISHER]

Gestational weight gain (GWG) has in numerous studies been associated with offspring birth weight (BW) and childhood weight. However, these associations might be explained by genetic confounding as offspring inherit their mother's genetic potential to gain weight. Furthermore, little is known about whether particular periods of pregnancy could influence offspring body weight differently. We therefore aimed to explore total and trimester-specific effects of GWG in monozygotic (MZ) twin mother-pairs on their offspring's BW, weight at 1 year and body mass index (BMI) at 5 and 10 years. MZ twin mothers born 1962–1975 were identified in national Swedish registers, and data on exposure and outcome variables was collected from medical records. We analyzed associations within and between twin pairs. We had complete data on the mothers’ GWG and offspring BW for 82 pairs. The results indicated that total, and possibly also second and third trimester GWG were associated with offspring BW within the twin pairs in the fully adjusted model (β = 0.08 z-score units, 95% CI: 0.001, 0.17; β = 1.32 z-score units, 95% CI: -0.29, 2.95; and β = 1.02 z-score units, 95% CI: -0.50, 2.54, respectively). Our findings, although statistically weak, suggested no associations between GWG and offspring weight or BMI during infancy or childhood. Our study suggests that total, and possibly also second and third trimester, GWG are associated with offspring BW when taking shared genetic and environmental factors within twin pairs into account. Larger family-based studies with long follow-up are needed to confirm our findings. [ABSTRACT FROM PUBLISHER]

BackgroundTwin studies have been criticized for upwardly biased estimates that might contribute to the missing heritability problem.MethodWe identified, from the general Swedish population born 1960–1990, informative sibships containing a proband, one reared-together full- or half-sibling and a full-, step- or half-sibling with varying degrees of childhood cohabitation with the proband. Estimates of genetic, shared and individual specific environment for drug abuse (DA), alcohol use disorder (AUD) and criminal behavior (CB), assessed from medical, legal or pharmacy registries, were obtained using Mplus.ResultsAggregate estimates of additive genetic effects for DA, AUD and CB obtained separately in males and females varied from 0.46 to 0.73 and agreed with those obtained from monozygotic and dizygotic twins from the same population. Of 54 heritability estimates from individual classes of informative sibling trios (3 syndromes × 9 classes of trios × 2 sexes), heritability estimates from the siblings were lower, tied and higher than those from obtained from twins in 26, one and 27 comparisons, respectively. By contrast, of 54 shared environmental estimates, 33 were lower than those found in twins, one tied and 20 were higher.ConclusionsWith adequate information, human populations can provide many methods for estimating genetic and shared environmental effects. For the three externalizing syndromes examined, concerns that heritability estimates from twin studies are upwardly biased or were not generalizable to more typical kinds of siblings were not supported. Overestimation of heritability from twin studies is not a likely explanation for the missing heritability problem. [ABSTRACT FROM AUTHOR]

By definition, monozygotic (MZ) twins carry an identical set of genetic information. The observation of early post-twinning mutational events was shown to cause phenotypic discordance among MZ twin pairs. These mutational events comprise genomic alterations at different scales, ranging from single nucleotide changes to larger copy-number variations (CNVs) of varying sizes, as well as epigenetic changes. Here, we performed whole-exome sequencing (WES) in nine discordant MZ twins to identify somatic mutational events in the affected twin that might exert a dominant negative effect. Five of these MZ twin pairs were discordant for congenital heart defects (CHD), two for endocrine disorders, one for omphalocele, and one for congenital diaphragmatic hernia (CDH). Analysis of WES data from all nine MZ twin pairs using the de novo probability tool DeNovoGear detected only one apparent de novo variation in TMPRSS13 in one of the CHD-affected twins. Analysis of WES data from all nine MZ twin pairs by using standard filter criteria without the de novo probability tool DeNovoGear revealed a total of 6,657 variations in which both the twin pairs differed. After filtering for variations only present in the affected twins and absent in in-house controls, 722 variations remained. Visual inspection for read quality decreased this number to 12, present only in the affected twin. However, Sanger sequencing of the overall 13 variations failed to confirm the variation in the affected twin. These results suggest that somatic mutational events in coding regions do not seem to play a major role in the phenotypic expression of MZ discordant twin pairs. [ABSTRACT FROM AUTHOR]

BackgroundAlcohol consumption is influenced by genetic factors. Previous studies have examined the heritability of alcohol consumption, or related phenotypes, from adolescence into adulthood, frequently finding that total heritability changes over time. However, it remains unclear whether the same genes underlie liability to alcohol consumption across development versus whether novel risk genes become important over time.MethodA population-based study of adult male twins (n=1790) born in Virginia, USA, retrospectively reported on their average monthly alcohol consumption from early adolescence through adulthood. We used twin modeling methods to explore genetic and environmental influences on alcohol consumption over time.ResultsOne latent genetic factor accounted for the majority of the heritability in alcohol consumption during mid- to late adolescence, but its influence declined thereafter; from young adulthood forward, heritability was largely attributable to a second genetic factor. The total heritability of alcohol consumption increased from 0 at ages 12–14 years to 0.40 by ages 18–21 years. Shared environmental factors declined in influence over time.ConclusionsThe heritability of alcohol consumption over time is dynamic both quantitatively and qualitatively. These results have important implications for gene identification endeavors. Furthermore, these findings could inform efforts to elucidate developmentally dynamic behaviors, such as antisocial behavior. [ABSTRACT FROM AUTHOR]

BackgroundAutism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and associated subclinical traits, regularly co-occur with one another. However, the aetiology of their co-occurrence remains poorly understood. This paper provides the first genetically informative, longitudinal analysis of the interaction between traits of ASD and ADHD, and explores their genetic and environmental overlap.MethodParents of approximately 5000 twin pairs completed questionnaires assessing traits of ASD and ADHD when twins were aged 8 and 12 years. Cross-lagged longitudinal modelling explored their developmental association, enabling a consideration of phenotypic-driven processes. Overlapping aetiological influences on traits at age 12 years were explored using bivariate twin modelling.ResultsTraits of ADHD at age 8 years were more strongly predictive of traits of ASD at 12 years than traits of ASD at 8 years were of traits of ADHD at 12 years. Analysis of traits by subscales assessing specific symptom domains suggested that communication difficulties were most strongly associated with traits of ADHD. Bivariate modelling suggested moderate genetic overlap on traits in males (genetic correlation = 0.41), and a modest degree of overlap in females (genetic correlation = 0.23) at age 12 years.ConclusionsTraits of ADHD at age 8 years significantly influence traits of ASD at age 12 years, after controlling for their initial relationship at age 8 years. In particular, early ADHD traits influenced later communication difficulties. These findings demonstrate the dynamic nature of co-occurring traits across development. In addition, these findings add to a growing body of literature suggesting that traits of ASD and ADHD may arise via similar aetiological processes. [ABSTRACT FROM AUTHOR]

Background. Intellectual deficits are commonly found in schizophrenia patients. These intellectual deficits have been found to be heritable. However, whether the intellectual deficits change over time and, if so, whether the change is related with an increased genetic risk for the disease are not known. Method. We investigated change of intelligence quotient (IQ) in a twin sample of chronically ill schizophrenia patients, the discordant co-twins and healthy controls during a follow-up period of 5 years. A total of 52 twins completed two IQ assessments: nine patients [three monozygotic (MZ) and six dizygotic (DZ)], 10 unaffected co-twins (three MZ and seven DZ) and 33 healthy control twins (21 MZ and 12 DZ). Results. A significant interaction effect over time was found between IQ measurement and illness (F = 4.22, df = 1, p < 0.05), indicating that change in IQ over time is significantly different between the groups. A stable course in IQ over time was found in the patients with schizophrenia (mean IQ from 109.78 at baseline to 108.44 at follow-up) relative to both the healthy control twins who showed a small increase (from 114.61 at baseline to 119.18 at follow- up) (t = 2.06, p<0.05) and the unaffected co-twins (from 111.60 to 117.60, t = -2.32, p<0.05). IQ change in the unaffected co-twins of schizophrenia patients was comparable with that in healthy control twins (t = -0.49, p = 0.63). Conclusions. Patients with schizophrenia in the chronic phase of the disease, but not the discordant co-twins, show a lack of increase in IQ, which is probably due to environmental (non-genetic) factors related to the disease. [ABSTRACT FROM AUTHOR]

BackgroundGays, lesbians and bisexuals (i.e. non-heterosexuals) have been found to be at much greater risk for many psychiatric symptoms and disorders, including depression. This may be due in part to prejudice and discrimination experienced by non-heterosexuals, but studies controlling for minority stress, or performed in very socially liberal countries, suggest that other mechanisms must also play a role. Here we test the viability of common cause (shared genetic or environmental etiology) explanations of elevated depression rates in non-heterosexuals.MethodA community-based sample of adult twins (n=9884 individuals) completed surveys investigating the genetics of psychiatric disorder, and were also asked about their sexual orientation. Large subsets of the sample were asked about adverse childhood experiences such as sexual abuse, physical abuse and risky family environment, and also about number of older brothers, paternal and maternal age, and number of close friends. Data were analyzed using the classical twin design.ResultsNon-heterosexual males and females had higher rates of lifetime depression than their heterosexual counterparts. Genetic factors accounted for 31% and 44% of variation in sexual orientation and depression respectively. Bivariate analysis revealed that genetic factors accounted for a majority (60%) of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were significant predictors of both sexual orientation and depression, further contributing to their correlation.ConclusionsNon-heterosexual men and women had elevated rates of lifetime depression, partly due to shared etiological factors, although causality cannot be definitively resolved. [ABSTRACT FROM PUBLISHER]

BackgroundEarly pubertal timing in girls is associated with elevated risk for dieting and eating pathology. The relative importance of biological versus socio-environmental mechanisms in explaining this association remains unclear. Moreover, these mechanisms may differ between objective measures of pubertal development and girls' subjective perceptions of their own maturation.MethodThe sample comprised 924 sister pairs from the National Longitudinal Study of Adolescent Health. Objective pubertal timing (menarcheal age), girls' perceptions of pubertal status and timing relative to peers, dieting and disordered eating behaviors were assessed during a series of confidential in-home interviews.ResultsBehavioral genetic models indicated that common genetic influences accounted for the association between early menarcheal age and increased risk for dieting in adolescence. In contrast, girls' subjective perceptions of their timing relative to peers were associated with dieting through an environmental pathway. Overall, subjective and objective measures of pubertal timing accounted for 12% of the variance in dieting.ConclusionsGenetic differences in menarcheal age increase risk for dieting among adolescent girls, while girls' perceptions of their maturation represent an environmentally mediated risk. [ABSTRACT FROM PUBLISHER]

Background: The normal development of cortisol regulation during childhood is thought to be influenced by a complex interplay between environmental and genetic factors.Method: The aim of this study was to estimate genetic and environmental influences on basal cortisol levels in a sample of 151 twin pairs aged 9-16 years. Salivary cortisol was collected on two consecutive days when the children attended school--immediately after awakening, 30 min post-awakening and at bedtime.Results: Heritability was highest (60%) for cortisol levels about 30 min after awakening. For samples taken immediately at awakening heritability was less pronounced (28%) and in the evening low (8%).Conclusion: The limited genetic influence on evening levels, moderate on cortisol at awakening and high on awakening response, might imply two genetic regulation patterns, one specifically for awakening response and one for the circadian rhythm proper. These findings could explain divergent results in previous studies and highlight the importance of taking the circadian rhythm into account in studies of cortisol levels in children. [ABSTRACT FROM AUTHOR]

The present study is the first to examine relationships between alexithymia and trait emotional intelligence (trait El 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 El 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing longitudinal twin study targeting all twins born in Sweden since July 1, 1992. Since 2004, parents of twins are interviewed regarding the children's somatic and mental health and social environment in connection with their 9th or 12th birthdays (CATSS-9/12). By January 2010, 8,610 parental interviews concerning 17,220 twins had been completed, with an overall response rate of 80%. At age 15 (CATSS-15) and 18 (CATSS-18), twins and parents complete questionnaires that, in addition to assessments of somatic and mental health, include measures of personality development and psychosocial adaptation. Twin pairs in CATSS-9/12 with one or both twins screening positive for autism spectrum disorders, attention deficit/hyperactivity disorder, tic disorders, developmental coordination disorder, learning disorders, oppositional defiant disorder, conduct disorder, obsessive–compulsive disorder, and/or eating problems have been followed with in-depth questionnaires on family, social environment and personality, and subsequently by clinical assessments at age 15 together with randomly selected population controls, including 195 clinically assessed twin pairs from the first 2 year cohorts (CATSS-15/DOGSS). This article describes the cohorts and study groups, data collection, and measures used. Prevalences, distributions, heritability estimates, ages at onset, and sex differences of mental health problems in the CATSS-9/12, that were analyzed and found to be overall comparable to those of other clinical and epidemiological studies. The CATSS study has the potential of answering important questions on the etiology of childhood mental health problems and their role in the development of later adjustment problems. [ABSTRACT FROM PUBLISHER]

Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans. [ABSTRACT FROM AUTHOR]

Sex differences in mental rotation ability have been observed in many countries. A previous study of Finnish participants reported that genetic and environmental influences on mental rotation ability differ between sexes. In this study, we assessed genetic and environmental influences on variance in mental rotation ability in 649 Japanese twins using a mental rotation test. To explain the influence of sex on variance in mental rotation ability, we applied genetic analysis using the sex limitation model. The following two factors explained variance in mental rotation ability: (1) the additive genetic factor, which reflects the accumulated small influence of many genes, and (2) the unique environmental factor, which is a type of environmental factor that differs between co-twins. The shared environmental factor, a type of environmental factor common for co-twins, could not explain the variance in mental rotation ability. Furthermore, the additive genetic factor was the same between sexes (i.e., not qualitative sex differences for the additive genetic factor), indicating that the same genes affect mental rotation ability in both sexes. Despite this observation, the additive genetic influence was greater in males than in females. In contrast, the unique environmental influence was not different between sexes. Considering the current results and those of a previous study, the quantitative sex difference for the additive genetic influences in mental rotation ability may be universal, while the unique environmental differences may depend on the characteristics of specific populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune disorder in which patients experience muscular fatigability due to the presence of anti-acetylcholine receptor (AChR) antibodies which inhibit signal transduction across the neuro-muscular junction. Like all complex disorders, disease is caused by an interaction between genetic and environmental factors. Although several genes have been identified which appear to be associated with MG, both classic twin studies and current multi-gene models are insufficient to explain either disease pathogenesis or inheritance. We examined the literature on MG to determine both mono- and dizygotic twin concordance rates, and used this data to (1) estimate the proportion of the population with underlying genetic predisposition to MG and the frequency of the environmental component and (2) derive the number of inherited genetic regions that are required to confer predisposition to MG. Using a MZ twin concordance rate of 35.5%, and a dizygotic rate of approximately 4-5% (based on family data), the probability of encountering environmental components necessary to develop MG in an individual with genetic predisposition is approximately 52.4%, making the frequency of predisposition (1:5240) roughly twice the rate of incidence. Furthermore, the number of genetic regions co-inherited between affected individuals is between two and four, which may be large haplotypes with interacting activity. Determining these haplotypes, by fully sequencing associated regions in cases and controls to identify mutations present, may therefore be a practically step toward the understanding of complex disease. [ABSTRACT FROM AUTHOR]

Molecular genetic research has provided some evidence for the association between depression and metabolic disorders. We sought to determine if molecular findings are reflected in twin analyses testing if common genetic and environmental risk factors contribute to the co-occurrence of diabetes and depression. Data to derive depression and diabetes were collected from 1,237 male-male twins who participated in the 2005 Vietnam Era Twin Study of Aging (VETSA). The 1,237 twins were comprised of 347 MZ pairs, 3 MZ singletons, 267 DZ pairs and 6 unpaired twins. Depression was defined as a score below 46 on the Short Form-36 mental component summary score. Diabetes was defined by self report, use of anti-diabetic medications and insulin. Twin models were fit to estimate the correlation of genetic and environmental contributions to depression and diabetes. Consistent with other studies these data support the association between depression and diabetes (OR = 1.7; 95%CI: 1.1-2.7). Genetic vulnerability accounted for 50% (95%CI: 32%-65%) of the variance in risk for depression and 69% (95%CI: 52%-81%) of the variance in risk for diabetes. The genetic correlation between depression and diabetes was r = 0.19 (95%CI: 0-0.46) and the non-shared environmental correlation was r = 0.09 (95% CI: 0-0.45). Overall there is little evidence that common genetic and environmental factors account for the co-occurrence of depression and diabetes in middle aged men. Further research in female twins and larger cohorts is warranted. [ABSTRACT FROM AUTHOR]

Absolute pitch is a rare pitch-naming ability with unknown etiology. Some scientists maintain that its manifestation depends solely on environmental factors, while others suggest that genetic factors contribute to it. We sought to further investigate the hypothesis that genetic factors support the acquisition of absolute pitch and to better elucidate the inheritance pattern of this trait. To this end, we conducted a twin study and a segregation analysis using data collected from a large population of absolute pitch possessors. The casewise concordance rate of 14 monozygotic twin pairs, 78.6%, was significantly different from that of 31 dizygotic twin pairs, 45.2%, assuming single ascertainment (x(2) = 5.57, 1 df, p = .018), supporting a role for genetics in the development of absolute pitch. Segregation analysis of 1463 families, assuming single ascertainment, produced a segregation ratio p(D) = .089 with SEp(D) = 0.006. Unlike an earlier segregation analysis on a small number of absolute pitch probands from musically educated families, our study indicates that absolute pitch is not inherited in a simple Mendelian fashion. Based on these data, absolute pitch is likely genetically heterogeneous, with environmental, epigenetic, and stochastic factors also perhaps contributing to its genesis. These findings are in agreement with the results of our recent linkage analysis. [ABSTRACT FROM AUTHOR]

The aim of this study was to quantify contributions of genetic and environmental factors to variation in timing of emergence of the primary teeth in a sample of monozygotic and dizygotic twins, using univariate model-fitting approaches. The sample comprised 94 pairs of monozygotic twins and 125 pairs of dizygous twins, all of European ancestry, aged from 2-6 years. Tooth emergence timing was based on parental report, with a subset of data validated by clinical assessment. Heritability estimates for tooth emergence timing were generally high, around 90%, however estimates for the lower right lateral incisor and the lower canines were around 50%. These findings confirm a strong genetic influence on observed variation in the timing of emergence of the human primary teeth. [ABSTRACT FROM AUTHOR]

The genetic and environmental contributions to determine digital dermatoglyphic traits were investigated by using female dizygotic and monozygotic twin pairs to estimate heritability indexes (h(2)). The evaluated sample was composed by 20 monozygotic twin pairs and 13 dizygotic twin pairs. A significant heritability (h(2) = 0.65 to 0.96) was observed for 12 dermatoglyphic characteristics (delta indexes and ridge counts for right hand, left hand and both hands, and ridge counts for most individual fingers). A negative correlation between the ridge counts and heritability indexes from individual fingers was found for the left hand, which appears to be associated to a higher arch pattern frequency in most left-hand fingers, since this frequency was negatively correlated with ridge counts and positively correlated with heritability indexes. Heritability indexes of right-hand fingers were positively correlated with loop pattern frequency and negatively correlated with whorl pattern frequency. The low heritability of ridge counts from left thumb, ring and little fingers (h(2) = 0.11 to 0.32) indicates a higher chance that the chorion type had an influence in the intra-pair variance of monozygotic twins. Results confirmed the predominant genetic influence on the total ridge count. The heritability indexes varied in up to 8 times between different fingers and its association to ridge counts and pattern frequency was very variable between hands, evidencing that the use of dermatoglyphic traits from individual fingers as indicators of genetic influences to other human traits should consider this variability. [ABSTRACT FROM AUTHOR]

Copy number variations (CNVs) are common structural variations in the human genome that strongly affect genomic diversity and can play a role in the development of several diseases, including neurodevelopmental disorders. Recent reports indicate that monozygotic twins can show differential CNV profiles. We searched CNVs in monozygotic twins discordant for schizophrenia to identify susceptible loci for schizophrenia. Three pairs of monozygotic twins discordant for schizophrenia were subjected to analysis. Genomic DNA samples were extracted from peripheral blood lymphocytes. We adopted the Affymetrix Genome-Wide Human SNP (Single Nucleotide Polymorphism) Array 6.0 to detect copy number discordance using Partek Genomics Suite 6.5 beta. In three twin pairs, however, validations by quantitative PCR and DNA sequencing revealed that none of the regions had any discordance between the three twin pairs. Our results support the hypothesis that epigenetic changes or fluctuation in developmental process triggered by environmental factors mainly contribute to the pathogenesis of schizophrenia. Schizophrenia caused by strong genetics factors including copy number alteration or gene mutation may be a small subset of the clinical population. [ABSTRACT FROM AUTHOR]

This study investigated phenotypic correlations between mental toughness and humor styles, as well as the common genetic and environmental effects underlying these correlations. Participants were 201 adult twin pairs from North America. They completed the Humor Styles Questionnaire, assessing individual differences in two positive (affiliative, self-enhancing) and two negative (aggressive, self-defeating) humor styles. They also completed the MT48, measuring individual differences in global mental toughness and its eight factors (Commitment, Control, Emotional Control, Control over Life, Confidence, Confidence in Abilities, Interpersonal Confidence, Challenge). Positive correlations were found between the positive humor styles and all of the mental toughness factors, with all but one reaching significance. Conversely, negative correlations were found between all mental toughness factors and the negative humor styles, with the mental toughness factors of Control, Emotional Control, Confidence, Confidence in Abilities, and Interpersonal Confidence exhibiting significant correlations. Subsequent behavioral genetic analyses revealed that these phenotypic correlations were primarily attributable to common genetic and common non-shared environmental factors. The implications of these findings regarding the potential effects of humor styles on wellbeing, and the possible selective use of humor by mentally tough individuals are discussed. [ABSTRACT FROM AUTHOR]

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 > R(G) > .98). These results indicate that head circumference is a highly heritable biometric trait and a valid target for future GWA studies. [ABSTRACT FROM AUTHOR]

Human height and body mass index are influenced by a large number of genes, each with small effects, along with environment. To identify common genetic variants associated with these traits, we performed genome-wide association studies in 11,536 individuals composed of Australian twins, family members, and unrelated individuals at approximately 550,000 genotyped SNPs. We identified a single genome-wide significant variant for height (P value=1.06x10(-9)) located in HHIP, a well-replicated height-associated gene. Suggestive levels of association were found for other known genes associated with height (P values<1x10(-6)): ADAMTSL3, EFEMP1, GPR126, and HMGA2; and BMI (P values<1x10(-4)): FTO and MC4R. Together, these variants explain less than 2% of total phenotypic variation for height and 0.5% for BMI. [ABSTRACT FROM AUTHOR]

Causes of individual differences in happiness, as assessed with the Subjective Happiness Scale, are investigated in a large of sample twins and siblings from the Netherlands Twin Register. Over 12,000 twins and siblings, average age 24.7 years (range 12 to 88), took part in the study. A genetic model with an age by sex design was fitted to the data with structural equation modeling in Mx. The heritability of happiness was estimated at 22% for males and 41% in females. No effect of age was observed. To identify the genomic regions contributing to this heritability, a genome-wide linkage study for happiness was conducted in sibling pairs. A subsample of 1157 offspring from 441 families was genotyped with an average of 371 micro-satellite markers per individual. Phenotype and genotype data were analyzed in MERLIN with multipoint variance component linkage analysis and age and sex as covariates. A linkage signal (logarithm of odds score 2.73, empirical p value 0.095) was obtained at the end of the long arm of chromosome 19 for marker D19S254 at 110 cM. A second suggestive linkage peak was found at the short arm of chromosome 1 (LOD of 2.37) at 153 cM, marker D1S534 (empirical p value of .209). These two regions of interest are not overlapping with the regions found for contrasting phenotypes (such as depression, which is negatively associated with happiness). Further linkage and future association studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract Miscarriage is the most common type of pregnancy loss, occurring in up to 15% of clinically recognized pregnancies. Our understanding of the etiology is still limited but is believed to be multifactorial, including endocrine and anatomical abnormalities, immunologic, genetic and lifestyle factors. The aim of this study was to explore whether genetic variability in miscarriage is under any genetic influence. 3234 MZ and DZ female twins completed postal self-completion questionnaires on pregnancies. Rates were adjusted for total number of pregnancies. The relative contribution of genetic and environmental factors to variation in miscarriage was assessed using twin intra-pair correlations and quantified using a variance components model fitting approach. We found 22.7% of our twins reporting having suffered at least one miscarriage. Current age, age at first pregnancy and higher number of pregnancies all had a significant influence on reported miscarriage. The concordance of miscarriage was similar in identical and non-identical twins, 26% and 27%, respectively. Shared environment and predominantly random error and unique environment rather than genetic factors best explained the total variation of miscarriage. To our knowledge, this is the first large twin study exploring heritability of miscarriage which unlike the vast majority of common variable traits, shows no significant genetic influence. In the absence of clear environmental factors, these results suggest the influence of random factors. [ABSTRACT FROM AUTHOR]

Recent studies in Asian populations have identified variants in the EDAR and FGFR2 genes that arose following the divergence of Asians and Europeans and are associated with thick straight hair. To date no genetic variants have been identified influencing hair texture in Europeans. In the current study we examined the heritability of hair curliness in three unselected samples of predominantly European ancestry (N(S1) = 2717; N(S2) = 3904; N(S3) = 5079). When rated using a three point scale (Straight/Wavy/Curly) males were approximately 5% more likely to report straight hair than females and there were suggestions in the data that curliness increased slightly with age. Across samples significant additive and dominant genetic influences were detected resulting in a broad sense heritability of 85-95%. Given the magnitude and the specificity of the EDAR effect on hair morphology in Asian populations we are hopeful that future association studies will detect similar genetic influences in European populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]