Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.

Monozygotic (MZ) twins form an important system for the study of biological plasticity in humans. While MZ twins are generally considered to be genetically identical, a number of studies have emerged that have demonstrated copy-number differences within a twin pair, particularly in those discordant for disease. The rate of autosomal copy-number variation (CNV) discordance within MZ twin pairs was investigated using a population sample of 376 twin pairs genotyped on Illumina Human610-Quad arrays. After CNV calling using both QuantiSNP and PennCNV followed by manual annotation, only a single CNV difference was observed within the MZ twin pairs, being a 130 KB duplication of chromosome 5. Five other potential discordant CNV were called by the software, but excluded based on manual annotation of the regions. It is concluded that large CNV discordance is rare within MZ twin pairs, indicating that any CNV difference found within phenotypically discordant MZ twin pairs has a high probability of containing the causal gene(s) involved.

Accurately identifying interactions between genetic vulnerabilities and environmental factors is of critical importance for genetic research on health and behavior. In the previous work of Van Hulle et al. (Behavior Genetics, Vol. 43, 2013, pp. 71–84), we explored the operating characteristics for a set of biometric (e.g., twin) models of Rathouz et al. (Behavior Genetics, Vol. 38, 2008, pp. 301–315), for testing gene-by-measured environment interaction (GxM) in the presence of gene-by-measured environment correlation (rGM) where data followed the assumed distributional structure. Here we explore the effects that violating distributional assumptions have on the operating characteristics of these same models even when structural model assumptions are correct. We simulated N = 2,000 replicates of n = 1,000 twin pairs under a number of conditions. Non-normality was imposed on either the putative moderator or on the ultimate outcome by ordinalizing or censoring the data. We examined the empirical Type I error rates and compared Bayesian information criterion (BIC) values. In general, non-normality in the putative moderator had little impact on the Type I error rates or BIC comparisons. In contrast, non-normality in the outcome was often mistaken for or masked GxM, especially when the outcome data were censored.

Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.

The relationship between self-report abilities and measured intelligence was examined at both the phenotypic (zero-order) level as well as at the genetic and environmental levels. Twins and siblings (N = 516) completed a timed intelligence test and a self-report ability questionnaire, which has previously been found to produce 10 factors, including: politics, interpersonal relationships, practical tasks, intellectual pursuits, academic skills, entrepreneur/business, domestic skills, vocal abilities, and creativity. At the phenotypic level, the correlations between the ability factor scores and intelligence ranged from 0.01 to 0.42 (between self-report academic abilities and verbal intelligence). Further analyses found that some of the phenotypic relationships between self-report ability scores and measured intelligence also had significant correlations at the genetic and environmental levels, suggesting that some of the observed relationships may be due to common genetic and/or environmental factors.

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role.

This study investigates the relative contribution of genetic and environmental factors to the stability of obsessive-compulsive (OC) symptoms in an adult population-based sample. We collected data from twin pairs and their siblings, using the Padua Inventory Revised Abbreviated, from the population-based Netherlands Twin Register (NTR) in 2002 (n = 10.134) and 2008 (n = 15.720). Multivariate twin analyses were used to estimate the stability of OC symptoms as a function of genetic and environmental components. OC symptoms were found to be highly stable, with a longitudinal phenotypic correlation of 0.63. Longitudinal broad sense heritability was found to be 56.0%. Longitudinal correlations for genetic (r = 0.58 for additive, r = 1 for non-additive genetic factors) and non-shared environment (r = 0.46) reflected stable effects, indicating that both genes and environment are influencing the stability of OC symptoms in adults. For the first time, evidence is reported for non-additive genetic effects on the stability of OC symptoms. In conclusion, this study showed that OC symptoms are highly stable across time in adults, and that genetic effects contribute mostly to this stability, both in an additive and non-additive way, besides non-shared environmental factors. These data are informative with respect to adult sample selection for future genetic studies, and suggest that gene–gene interaction studies are needed to further understand the dominance effect found in this study.

Breastfeeding has been an important survival trait during human history, though it has long been recognized that individuals differ in their exact breastfeeding behavior. Here our aims were, first, to explore to what extent genetic and environmental influences contributed to the individual differences in breastfeeding behavior; second, to detect possible genetic variants related to breastfeeding; and lastly, to test if the genetic variants associated with breastfeeding have been previously found to be related with breast size. Data were collected from a large community-based cohort of Australian twins, with 3,364 women participating in the twin modelling analyses and 1,521 of them included in the genome-wide association study (GWAS). Monozygotic (MZ) twin correlations (r MZ = 0.52, 95% CI 0.46–0.57) were larger than dizygotic (DZ) twin correlations (r DZ = 0.35, 95% CI 0.25–0.43) and the best-fitting model was the one composed by additive genetics and unique environmental factors, explaining 53% and 47% of the variance in breastfeeding behavior, respectively. No breastfeeding-related genetic variants reached genome-wide significance. The polygenic risk score analyses showed no significant results, suggesting breast size does not influence breastfeeding. This study confers a replication of a previous one exploring the sources of variance of breastfeeding and, to our knowledge, is the first one to conduct a GWAS on breastfeeding and look at the overlap with variants for breast size.

Systolic and diastolic blood pressure, pulse pressure (PP), and body mass index (BMI) are heritable traits in human metabolic health but their common genetic and environmental backgrounds are not well investigated. The aim of this article was to explore the phenotypic and genetic associations among PP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. The studied sample contained 615 twin pairs (17–84 years) collected in the Qingdao municipality. Univariate and multivariate structural equation models were fitted for assessing the genetic and environmental contributions. The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for each four phenotypes. Heritability estimated in univariate analysis ranged from 0.42 to 0.74 with the highest for BMI (95% CI 0.70–0.78), and the lowest for PP (95% CI 0.34–0.49). The multivariate model estimated (1) high genetic correlations for DBP with SBP (0.87), PP with SBP (0.75); (2) low–moderate genetic correlations between PP and DBP (0.32), each BP component and BMI (0.24–0.37); (3) moderate unique environmental correlation for PP with SBP (0.68) and SBP with DBP (0.63); (4) there was no significant unique environmental correlation between PP and BMI. Overall, our multivariate analyses revealed common genetic and environmental backgrounds for PP, BP, and BMI in Chinese twins.

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.

Gene-based tests such as versatile gene-based association study (VEGAS) are commonly used following per-single nucleotide polymorphism (SNP) GWAS (genome-wide association studies) analysis. Two limitations of VEGAS were that the HapMap2 reference set was used to model the correlation between SNPs and only autosomal genes were considered. HapMap2 has now been superseded by the 1,000 Genomes reference set, and whereas early GWASs frequently ignored the X chromosome, it is now commonly included. Here we have developed VEGAS2, an extension that uses 1,000 Genomes data to model SNP correlations across the autosomes and chromosome X. VEGAS2 allows greater flexibility when defining gene boundaries. VEGAS2 offers both a user-friendly, web-based front end and a command line Linux version. The online version of VEGAS2 can be accessed through https://vegas2.qimrberghofer.edu.au/. The command line version can be downloaded from https://vegas2.qimrberghofer.edu.au/zVEGAS2offline.tgz. The command line version is developed in Perl, R and shell scripting languages; source code is available for further development.

We analyzed the effect of total fertility rate (TFR) and crude birth rate (CBR) on the number of males per 100 females at birth, also called the secondary sex ratio (SR), and on the twinning rate (TWR). Earlier studies have noted regional variations in TWR and racial differences in the SR. Statistical analyses have shown that comparisons between SRs demand large data sets because random fluctuations in moderate data are marked. Consequently, reliable results presuppose national birth data. Here, we analyzed historical demographic data and their regional variations between counties in Sweden. We built spatial models for the TFR in 1860 and the CBR in 1751–1870, and as regressors we used geographical coordinates for the provincial capitals of the counties. For both variables, we obtained significant spatial variations, albeit of different patterns and power. The SR among the live-born in 1749–1869 and the TWR in 1751–1860 showed slight spatial variations. The influence of CBR and TFR on the SR and TWR was examined and statistical significant effects were found.

The study endeavored to assess the epidemiology, postnatal survival, and growth pattern of multiple births in Sub-Saharan Africa (SSA). It was based on the data of 25 demographic health surveys conducted in the subcontinent since 2008. The records of 213,889 children born in the preceding 59 months of the surveys were included. The multiple birth rate was computed as the number of multiple confinements per 1,000 births. Factors associated with multiple births were identified using logistic regression and their survival pattern was assessed using the Kaplan–Meier method. The multiple birth rate was 17.1 (95% confidence interval: 17.7–16.6) and showed considerable variation across the 25 countries included in the study. Odds of multiple births were significantly increased with advanced maternal age, parity, and maternal height but not with wealth index, age at first birth, and month of birth. At the end of the fourth year of age, the cumulative survival probability was as low as 0.77 in multiple births as compared to 0.93 in their counterparts. The odds of neonatal, infant and under-five mortality were 5.55, 4.39, and 3.72 times increased in multiple births, respectively. Multiple births tend to be malnourished than singletons and the odds of wasting, stunting, and underweight were 1.31, 1.83, and 1.73 times raised, consecutively. Nevertheless, multiple births regain their weight-for-age (WFA) and height-for-age (HFA) deficits by the end of the fourth year of age. Counseling pregnant mothers with multiple gestation to give birth at a health institution and providing close medical follow-up during and after the neonatal period can improve the survival of multiple births.

Highlights from the 15th International Congress of Twin Studies are presented. The congress was held November 16–19, 2014 in Budapest, Hungary. This report is followed by summaries of research addressing the differentiation of MZ co-twins by single nucleotide polymorphisms (SNPs), an unusual error in infant twin-singleton hospital registration, twins with childhood-onset narcolepsy with cataplexy, and the parenting effects of hearing loss in one co-twin. Media interest in twins covers a new Broadway musical based on the conjoined twins Violet and Daisy Hilton, male twins becoming famous in fashion, twins who turned 102 and unique insights from a conjoined twin survivor.