Recently, Macgregor et al. (2009) demonstrated significant associations of ADH polymorphisms with reactions to alcohol and alcohol consumption measures in an Australian sample. The aim of the present study was to replicate these findings in a Dutch sample. Survey data on alcohol phenotypes came from 1,754 unrelated individuals registered with the Netherlands Twin Register. SNPs in the ADH gene cluster located on chromosome 4q (n = 491) were subdivided in seven gene sets: ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of SNPs with alcohol consumption measures, age at onset variables, reactions to alcohol and problem drinking liability were examined. Of the original 38 SNPs studied by Macgregor et al. (2009), six SNPs were not available in our dataset, because one of them had a minor allele frequency < .01 (rs1229984) and five could not be imputed. The remaining SNP associations with alcohol phenotypes as identified by Macgregor et al. (2009) were not replicated in the Dutch sample, after correcting for multiple genotype and phenotype testing. Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that is in strong LD with rs6827292. Furthermore, an association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was observed. No significant associations were found for alcohol consumption and problem drinking liability. Although these findings do not replicate the earlier findings at the SNP level, the results confirm the role of the ADH gene cluster in alcohol phenotypes.

The purpose of this study is to compare obstetric and birthweight data of twin children from the two largest databases in Japan to estimate the difference between them in sample collection. The first group consisted of 1131 twin-pair school applicants, and the second group consisted of members' children from several maternal associations devoted to twins and included 951 pairs. All data were gathered by questionnaire. The mean birth years of the twins in these two databases were 1979 and 1995 respectively. The percentage of mothers treated with ovulation-stimulating drugs or in-vitro fertilization was markedly higher in the maternal associations group. Gestational age was around 1 week less in the maternal associations group, whereas birthweight according to gestational weeks and intrapair relative birth weight difference as a percentage according to zygosity showed little difference between both groups. We conclude that the obstetric and birthweight feature data from both groups should be considered to construct twin growth charts based on the methods of sample selection.

Twin studies have found that ~50% of variance in electrocardiogram (ECG) traits can be explained by genetic factors. However, genetic variants identified through genome-wide association studies explain less than 10% of the total trait variability. Some have argued that the equal environment assumption for the classical twin model might be invalid, resulting in inflated narrow-sense heritability (h2) estimates, thus explaining part of the ‘missing h2’. Genomic relatedness restricted maximum likelihood (GREML) estimation overcomes this issue. This method uses both family data and genome-wide coverage of common SNPs to determine the degree of relatedness between individuals to estimate both h2 explained by common SNPs and total h2. The aim of the current study is to characterize more reliably than previously possible ECG trait h2 using GREML estimation, and to compare these outcomes to those of the classical twin model. We analyzed ECG traits (heart rate, PR interval, QRS duration, RV5+SV1, QTc interval, Sokolow-Lyon product, and Cornell product) in up to 3,133 twins from the TwinsUK cohort and derived h2 estimates by both methods. GREML yielded h2 estimates between 47% and 68%. Classical twin modeling provided similar h2 estimates, except for the Cornell product, for which the best fit included no genetic factors. We found no evidence that the classical twin model leads to inflated h2 estimates. Therefore, our study confirms the validity of the equal environment assumption for monozygotic and dizygotic twins and supports the robust basis for future studies exploring genetic variants responsible for the variance of ECG traits.

The chromosome 8q24 region (specifically, 8q24.21.a) is known to harbor variants associated with risk of breast, colorectal, prostate, and bladder cancers. In 2008, variants rs10505477 and rs6983267 in this region were associated with increased risk of invasive ovarian cancer (p < 0.01); however, three subsequent ovarian cancer reports of 8q24 variants were null. Here, we used a multi-site case-control study of 940 ovarian cancer cases and 1,041 controls to evaluate associations between these and other single-nucleotide polymorphisms (SNPs) in this 8q24 region, as well as in the 9p24 colorectal cancer associated-region (specifically, 9p24.1.b). A total of 35 SNPs from previous reports and additional tagging SNPs were assessed using an Illumina GoldenGate array and analyzed using logistic regression models, adjusting for population structure and other potential confounders. We observed no association between genotypes and risk of ovarian cancer considering all cases, invasive cases, or invasive serous cases. For example, at 8q24 SNPs rs10505477 and rs6983267, analyses yielded per-allele invasive cancer odds ratios of 0.95 (95% confidence interval (CI) 0.82–1.09, p trend 0.46) and 0.97 (95% CI 0.84–1.12, p trend 0.69), respectively. Analyses using an approach identical to that of the first positive 8q24 report also yielded no association with risk of ovarian cancer. In the 9p24 region, no SNPs were associated with risk of ovarian cancer overall or with invasive or invasive serous disease (all p values > 0.10). These results indicate that the SNPs studied here are not related to risk of this gynecologic malignancy and that the site-specific nature of 8q24.21.a associations may not include ovarian cancer.

This study examined the association between early child care on the development of behavior problems. At the age of 5 years, child care information was collected from parents on a large group of twins who were born between 1985 and 1997. Mothers and fathers rated the behavior of the child at ages 3, 7, and 10 years using the Child Behavior Checklist (CBCL) and teachers reported on the same children's behaviors using the Teacher's Report Form (TRF) at ages 7 and 10. At the age of 3 years, children with nonparental child care experiences had more externalizing problems than children with only parental child care. The long-term effects of quantity of child care were mixed and were only significant for mother ratings and for children from families with a low socioeconomic status. Overall, the effect sizes of child care were very small (effect sizes were between .12 and .23). Children with a larger amount of child care did not show more behavior problems, therefore it was questioned whether the increased levels of behavior problems could be attributed to quantity of child care.

Male twin gestations exhibit higher incidence of fetal morbidity and mortality than singleton gestations. From an evolutionary perspective, the relatively high rates of infant and child mortality among male twins born into threatening environments reduce the fitness of these gestations, making them more vulnerable to fetal loss. Women do not perceive choosing to spontaneously abort gestations although the outcome may result from estimates, made without awareness, of the risks of continuing a pregnancy. Here, we examine whether the non-conscious decisional biology of gestation can be linked to conscious risk aversion. We test this speculation by measuring the association between household surveys in Sweden that gauge financial risk aversion in the population and the frequency of twins among live male births. We used time-series regression methods to estimate our suspected associations and Box–Jenkins modeling to ensure that autocorrelation did not confound the estimation or reduce its efficiency. We found, consistent with theory, that financial risk aversion in the population correlates inversely with the odds of a twin among Swedish males born two months later. The odds of a twin among males fell by approximately 3.5% two months after unexpectedly great risk aversion in the population. This work implies that shocks that affect population risk aversion carry implications for fetal loss in vulnerable twin pregnancies.

Acne vulgaris is a skin disease with a multifactorial and complex pathology. While several twin studies have estimated that acne has a heritability of up to 80%, the genomic elements responsible for the origin and pathology of acne are still undiscovered. Here we performed a twin-based structural equation model, using available data on acne severity for an Australian sample of 4,491 twins and their siblings aged from 10 to 24. This study extends by a factor of 3 an earlier analysis of the genetic factors of acne. Acne severity was rated by nurses on a 4-point scale (1 = absent to 4 = severe) on up to three body sites (face, back, chest) and on up to three occasions (age 12, 14, and 16). The phenotype that we analyzed was the most severe rating at any site or age. The polychoric correlation for monozygotic twins was higher (rMZ = 0.86, 95% CI [0.81, 0.90]) than for dizygotic twins (rDZ = 0.42, 95% CI [0.35, 0.47]). A model that includes additive genetic effects and unique environmental effects was the most parsimonious model to explain the genetic variance of acne severity, and the estimated heritability was 0.85 (95% CI [0.82, 0.87]). We then conducted a genome-wide analysis including an additional 271 siblings — for a total of 4,762 individuals. A genome-wide association study (GWAS) scan did not detect loci associated with the severity of acne at the threshold of 5E-08 but suggestive association was found for three SNPs: rs10515088 locus 5q13.1 (p = 3.9E-07), rs12738078 locus 1p35.5 (p = 6.7E-07), and rs117943429 locus 18q21.2 (p = 9.1E-07). The 5q13.1 locus is close to PIK3R1, a gene that has a potential regulatory effect on sebocyte differentiation.

Objective: Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. Method: We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Results: Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. Conclusions: There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

Meta-analyses suggest that clinical psychopathology is preceded by dimensional behavioral and cognitive phenotypes such as psychotic experiences, executive functioning, working memory and affective dysregulation that are determined by the interplay between genetic and nongenetic factors contributing to the severity of psychopathology. The liability to mental ill health can be psychometrically measured using experimental paradigms that assess neurocognitive processes such as salience attribution, sensitivity to social defeat and reward sensitivity. Here, we describe the TwinssCan, a longitudinal general population twin cohort, which comprises 1202 individuals (796 adolescent/young adult twins, 43 siblings and 363 parents) at baseline. The TwinssCan is part of the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia project and recruited from the East Flanders Prospective Twin Survey. The main objective of this project is to understand psychopathology by evaluating the contribution of genetic and nongenetic factors on subclinical expressions of dimensional phenotypes at a young age before the onset of disorder and their association with neurocognitive processes, such as salience attribution, sensitivity to social defeat and reward sensitivity.

Objective: The human gut microbiota has been demonstrated to be associated with a number of host phenotypes, including obesity and a number of obesity-associated phenotypes. This study is aimed at further understanding and describing the relationship between the gut microbiota and obesity-associated measurements obtained from human participants. Subjects/Methods: Here, we utilize genetically informative study designs, including a four-corners design (extremes of genetic risk for BMI and of observed BMI; N = 50) and the BMI monozygotic (MZ) discordant twin pair design (N = 30), in order to help delineate the role of host genetics and the gut microbiota in the development of obesity. Results: Our results highlight a negative association between BMI and alpha diversity of the gut microbiota. The low genetic risk/high BMI group of individuals had a lower gut microbiota alpha diversity when compared to the other three groups. Although the difference in alpha diversity between the lean and heavy groups of the BMI-discordant MZ twin design did not achieve significance, this difference was observed to be in the expected direction, with the heavier participants having a lower average alpha diversity. We have also identified nine OTUs observed to be associated with either a leaner or heavier phenotype, with enrichment for OTUs classified to the Ruminococcaceae and Oxalobacteraceae taxonomic families. Conclusion: Our study presents evidence of a relationship between BMI and alpha diversity of the gut microbiota. In addition to these findings, a number of OTUs were found to be significantly associated with host BMI. These findings may highlight separate subtypes of obesity, one driven by genetic factors, the other more heavily influenced by environmental factors.

Our current society is characterized by an increased availability of industrially processed foods with high salt, fat and sugar content. How is it that some people prefer these unhealthy foods while others prefer more healthy foods? It is suggested that both genetic and environmental factors play a role. The aim of this study was to (1) identify food preference clusters in the largest twin-family study into food preference to date and (2) determine the relative contribution of genetic and environmental factors to individual differences in food preference in the Netherlands. Principal component analysis was performed to identify the preference clusters by using data on food liking/disliking from 16,541 adult multiples and their family members. To estimate the heritability of food preference, the data of 7833 twins were used in structural equation models. We identified seven food preference clusters (Meat, Fish, Fruits, Vegetables, Savory snacks, Sweet snacks and Spices) and one cluster with Drinks. Broad-sense heritability (additive [A] + dominant [D] genetic factors) for these clusters varied between .36 and .60. Dominant genetic effects were found for the clusters Fruit, Fish (males only) and Spices. Quantitative sex differences were found for Meat, Fish and Savory snacks and Drinks. To conclude, our study convincingly showed that genetic factors play a significant role in food preference. A next important step is to identify these genes because genetic vulnerability for food preference is expected to be linked to actual food consumption and different diet-related disorders.

The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.

The reported genetic correlation of 1.0 between the traits of procrastination and impulsivity (Gustavson, D. E., Miyake, A., Hewitt, J. K., & Friedman, N. P. (2014). Psychological Science), which was held to support an evolutionary origin of the relationship between the two traits, was tested in data from two large samples of twins from Australia. A genetic correlation of 0.299 was obtained. It was concluded that, although the presence of a genetic correlation between the two traits was supported, the modest magnitude of the correlation was such as to be consistent with many possible hypotheses, evolutionary and otherwise, about causal relationships between the traits in question.

Evidence of a positive association between birthweight and IQ has been established in several studies. Analyses of within twin pair differences in birthweight and IQ have been used to shed light on the basis of the association. The strength of this approach is the possibility of controlling for both unmeasured common childhood–environmental factors as well as genetic factors shared by the co-twins. Two twin studies suggest the existence of genetic mediation between birthweight and IQ, that is, common genetic factors influence both fetal growth and IQ in childhood, while two other twin studies find no evidence of such mediation. In the present study we use a large population-based national register study of 2,413 Danish twin-pairs from birth cohorts 1986–1990, of which we have zygosity information on 74%. We perform individual level as well as intra-pair analyses of birthweight and school achievements at age 16. For both sexes we observed a monotonic increase in academic performance with increasing percentiles of birthweight. However, we did not find that this association is due to genetic mediation.

Twin designs, comparing correlations in monozygotic (MZ) versus dizygotic (DZ) twins, have an extensive history. One major confounder in such studies is that MZ twins may share postnatal environmental influences more so than do DZ twins. To avoid such confounding, twins separated at or soon after birth have been studied, but their scarcity often makes this approach impractical. Another method has been to measure the degree of contact twins have maintained over time, and adjust the observed correlations. Here, we remove confounding by utilizing the discrepancy between biological and self-perceived zygosity to separate environmental from genetic sources of twin similarity. We analyzed dietary patterns and physiologic traits in 350 female twin pairs of the 1988 Kaiser Permanente Twin Registry. Among twin pairs, 175 were MZ by self-report and genetic testing (MZC), 136 were DZ by self-report and genetic testing (DZC), 30 were MZ by genetic testing but not by self-report (MZW), and 9 were DZ by genetic testing but not by self-report (DZW) but were excluded due to small sample size. For healthy food patterns, MZC and MZW intraclass correlations were similar and greater than for DZC, yielding positive and significant heritability estimates. For unhealthy food patterns, the MZC, MZW and DZC correlations were similar with no significant heritability. For physiologic traits, MZC and MZW correlations were similar and higher than those for DZC, indicating significant heritability, except for insulin for which MZW and DZC were similar and which showed modest heritability. Twins of mistaken zygosity (TOMZ) provides a useful approach to robust determination of heritability.

In many Western countries, women now reach educational levels comparable to men, although their income remains considerably lower. For the past decades, it has become increasingly clear that these measures of socio-economic status are influenced by genetic as well as environmental factors. Less is known about the relationship between education and income, and sex differences. The aim of this study was to explore genetic and environmental factors influencing education and income in a large cohort of young Norwegian twins, with special emphasis on gender differences. National register data on educational level and income were obtained for 7,710 twins (aged 29–41 years). Bivariate Cholesky models were applied to estimate qualitative and quantitative gender differences in genetic and environmental influences, the relative contribution of genetic and environmental factors to the correlation between education and income, and genetic correlations within and between sexes and phenotypes. The phenotypic correlation between educational level and income was 0.34 (0.32–0.39) for men and 0.45 (0.43–0.48) for women. An ACE model with both qualitative and quantitative sex differences fitted the data best. The genetic correlation between men and women (rg) was 0.66 (0.22–1.00) for educational attainment and 0.38 (0.01–0.75) for income, and between the two phenotypes 0.31 (0.08–0.52) for men and 0.72 (0.64–0.85) for women. Our results imply that, in relatively egalitarian societies with state-supported access to higher education and political awareness of gender equality, genetic factors may play an important role in explaining sex differences in the relationship between education and income.

Hostility has been shown to be a vulnerability marker for various health problems. The present study examined genetic and environmental contributions to individual differences in hostility in South Korean adolescent and young adult twins. Seven hundred and nineteen same- and opposite-sex twin pairs aged from 13 to 23 years completed a hostility scale. The scalar sex-limitation model was applied to the data. The best fitting model indicated that 34% of the total variation of hostility was attributable to genetic factors operating in a nonadditive manner. The remaining 66% of the variance was associated with nonshared environmental influences and measurement error. These findings were largely consistent with results from previous twin studies of personality based on Caucasian twins, rendering support for the pervasive influence of genetic non-additivity on human personality traits and the generalization of the heritability of personality across human populations.

While preterm birth and restricted fetal growth are strongly associated with infant mortality, the extent to which these associations are modified by placental abruption remains unknown. A retrospective cohort study was carried out to examine the risk of infant mortality among twins in relation to abruption, and explore the independent contributions of preterm birth and restricted fetal growth to these associations. The study was restricted to women who had delivered twins at 22 weeks' gestation or more and fetuses weighing 500 grams or more in the United States (1989–2000). Risks of preterm birth (less than 37 weeks' gestation), fetal growth restriction and infant mortality, in relation to placental abruption, were evaluated. All analyses were adjusted for potential sociodemographic confounding factors. The association between restricted twin fetal growth and abruption was the strongest among the most severely growth-restricted babies (i.e., less than 1 centile), with the strength of association diminishing with increasing birthweight centiles. The risk of preterm birth among pregnancies with and without abruption were 80.1% and 51.9%, respectively (relative risk [RR] 1.5, 95% confidence interval [CI] 1.4–1.6). The risk of small-for-gestational-age (SGA; birthweight of less than the 10th centile for gestational age) among abruption and nonabruption births was 11.7% and 9.2%, respectively (RR 1.3, 95% CI 1.2–1.4). Compared with twins of the appropriate growth delivered at term, the relative risks for infant mortality in the presence of abruption were 9.9 (95% CI 5.4–18.2) for term-SGA, 25.0 (95% CI 22.3–28.1) for preterm-non-SGA, and 36.2 (95% CI 28.4–46.1) for preterm-SGA births. The association between infant mortality and abruption among twins appears largely mediated through preterm birth, and to a lesser extent, through SGA. The association between fetal growth and abruption is strongest among the severely growth-restricted babies, suggesting that the origins of placental abruption may develop in early pregnancy.

Individuals who experience one type of trauma often experience other types, yet few studies have examined the clustering of trauma. This study examines the clustering of traumatic events and associations of trauma with risk for single and co-occurring major depressive disorder (MDD) and panic attack for 20 years after first trauma. Lifetime histories of MDD, panic attack, and traumatic events were obtained from participants in an Australian twin sample. Latent class analysis was used to derive trauma classes based on each respondent's trauma history. Associations of the resulting classes and of parental alcohol problems and familial effects with risk for a first onset of single and co-occurring MDD and panic attack were examined from the year of first trauma to 20 years later. Traumatic events clustered into three distinct classes characterized by endorsement of little or no trauma, primarily nonassaultive, and primarily assaultive events. Individuals in the assaultive class were characterized by a younger age at first trauma, a greater number of traumatic events, and high rates of parental alcohol problems. Members of the assaultive trauma class had the strongest and most enduring risk for single and co-occurring lifetime MDD and panic attack. Assaultive trauma outweighed associations of familial effects and nonassaultive trauma with risk for 10 years following first trauma.

To obtain a better understanding of how genetic and environmental processes are involved in the stability and change in problem behavior from early adolescence into adulthood, studies with genetically informative samples are important. The present study used parent-reported data on internalizing and externalizing problem behavior of adoptees at mean ages 12.4, 15.5 and 26.3. In this adoption study adopted biologically related sibling pairs shared on average 50% of their genes and were brought up in the same family environment, whereas adopted biologically unrelated sibling pairs only shared their family environment. The resemblance between these adopted biologically related (N = 106) and unrelated sibling pairs (N = 230) was compared and examined over time. We aimed to investigate (1) to what extent are internalizing and externalizing problem behavior stable from early adolescence into adulthood, and (2) whether the same or different genetic and environmental factors affect these problem behaviors at the 3 assessments. Our results show that both internalizing (rs ranging from .34 to .58) and externalizing behavior (rs ranging from .47 to .69) were rather stable over time. For internalizing and externalizing problem behavior it was found that both genetic and shared environmental influences could be modeled by an underlying common factor, which explained variance in problem behavior from early adolescence into adulthood and accounted for stability over time. The nonshared environmental influences were best modeled by a Cholesky decomposition for internalizing behavior, whereas a time-specific influence of the nonshared environment was included in the final model of externalizing behavior.